Association between Daytime Napping and Chronic Diseases in China.

PubMed

Zhou, Junmin; Kessler, Asia Sikora; Su, Dejun

2016-03-01

To explore the relationship between daytime napping and incidence of chronic diseases over the past 6 months among adults in China. Based on data collected from 13,469 respondents over age 40 in the Chinese Family Panel Studies in 2010, logistic regression models were estimated to examine the association between daytime napping and the incidence of any chronic diseases and 3 specific chronic diseases (hypertension, diabetes, and heart disease) after adjusting for confounders. Differences of risks by sex and age were also investigated. In the sample, 50.8% were women and 32.2% were over 60 years old. Adjusted estimates show respondents with daytime napping had elevated odds of developing any chronic diseases, hypertension, and diabetes compared to those who did not nap; having over 60 minutes of daytime napping had weaker association compared with shorter duration of daytime napping. The association between daytime napping and hypertension was found in women but not in men. Daytime napping appears to be associated with elevated risk of incidence of any chronic diseases, hypertension, and diabetes.

Characterization of a Linked Jumonji Domain of the KDM5/JARID1 Family of Histone H3 Lysine 4 Demethylases.

PubMed

Horton, John R; Engstrom, Amanda; Zoeller, Elizabeth L; Liu, Xu; Shanks, John R; Zhang, Xing; Johns, Margaret A; Vertino, Paula M; Fu, Haian; Cheng, Xiaodong

2016-02-05

The KDM5/JARID1 family of Fe(II)- and α-ketoglutarate-dependent demethylases remove methyl groups from tri- and dimethylated lysine 4 of histone H3. Accumulating evidence from primary tumors and model systems supports a role for KDM5A (JARID1A/RBP2) and KDM5B (JARID1B/PLU1) as oncogenic drivers. The KDM5 family is unique among the Jumonji domain-containing histone demethylases in that there is an atypical insertion of a DNA-binding ARID domain and a histone-binding PHD domain into the Jumonji domain, which separates the catalytic domain into two fragments (JmjN and JmjC). Here we demonstrate that internal deletion of the ARID and PHD1 domains has a negligible effect on in vitro enzymatic kinetics of the KDM5 family of enzymes. We present a crystal structure of the linked JmjN-JmjC domain from KDM5A, which reveals that the linked domain fully reconstitutes the cofactor (metal ion and α-ketoglutarate) binding characteristics of other structurally characterized Jumonji domain demethylases. Docking studies with GSK-J1, a selective inhibitor of the KDM6/KDM5 subfamilies, identify critical residues for binding of the inhibitor to the reconstituted KDM5 Jumonji domain. Further, we found that GSK-J1 inhibited the demethylase activity of KDM5C with 8.5-fold increased potency compared with that of KDM5B at 1 mm α-ketoglutarate. In contrast, JIB-04 (a pan-inhibitor of the Jumonji demethylase superfamily) had the opposite effect and was ~8-fold more potent against KDM5B than against KDM5C. Interestingly, the relative selectivity of JIB-04 toward KDM5B over KDM5C in vitro translates to a ~10-50-fold greater growth-inhibitory activity against breast cancer cell lines. These data define the minimal requirements for enzymatic activity of the KDM5 family to be the linked JmjN-JmjC domain coupled with the immediate C-terminal helical zinc-binding domain and provide structural characterization of the linked JmjN-JmjC domain for the KDM5 family, which should prove useful in the

Benefits of napping in healthy adults: impact of nap length, time of day, age, and experience with napping.

PubMed

Milner, Catherine E; Cote, Kimberly A

2009-06-01

Napping is a cross-cultural phenomenon which occurs across the lifespan. People vary widely in the frequency with which they nap as well as the improvements in alertness and well-being experienced. The systematic study of daytime napping is important to understand the benefits in alertness and performance that may be accrued from napping. This review paper investigates factors that affect the benefits of napping such as duration and temporal placement of the nap. In addition, the influence of subject characteristics such as age and experience with napping is examined. The focus of the review is on benefits for healthy individuals with regular sleep/wake schedules rather than for people with sleep or medical disorders. The goal of the review is to summarize the type of performance improvements that result from napping, critique the existing studies, and make recommendations for future research.

Biochemical reconstitution and phylogenetic comparison of human SET1 family core complexes involved in histone methylation.

PubMed

Shinsky, Stephen A; Monteith, Kelsey E; Viggiano, Susan; Cosgrove, Michael S

2015-03-06

Mixed lineage leukemia protein-1 (MLL1) is a member of the SET1 family of histone H3 lysine 4 (H3K4) methyltransferases that are required for metazoan development. MLL1 is the best characterized human SET1 family member, which includes MLL1-4 and SETd1A/B. MLL1 assembles with WDR5, RBBP5, ASH2L, DPY-30 (WRAD) to form the MLL1 core complex, which is required for H3K4 dimethylation and transcriptional activation. Because all SET1 family proteins interact with WRAD in vivo, it is hypothesized they are regulated by similar mechanisms. However, recent evidence suggests differences among family members that may reflect unique regulatory inputs in the cell. Missing is an understanding of the intrinsic enzymatic activities of different SET1 family complexes under standard conditions. In this investigation, we reconstituted each human SET1 family core complex and compared subunit assembly and enzymatic activities. We found that in the absence of WRAD, all but one SET domain catalyzes at least weak H3K4 monomethylation. In the presence of WRAD, all SET1 family members showed stimulated monomethyltransferase activity but differed in their di- and trimethylation activities. We found that these differences are correlated with evolutionary lineage, suggesting these enzyme complexes have evolved to accomplish unique tasks within metazoan genomes. To understand the structural basis for these differences, we employed a "phylogenetic scanning mutagenesis" assay and identified a cluster of amino acid substitutions that confer a WRAD-dependent gain-of-function dimethylation activity on complexes assembled with the MLL3 or Drosophila trithorax proteins. These results form the basis for understanding how WRAD differentially regulates SET1 family complexes in vivo. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Mandatory Nap Times and Group Napping Patterns in Child Care: An Observational Study.

PubMed

Staton, Sally L; Smith, Simon S; Hurst, Cameron; Pattinson, Cassandra L; Thorpe, Karen J

2017-01-01

Policy provision for naps is typical in child care settings, but there is variability in the practices employed. One practice that might modify children's early sleep patterns is the allocation of a mandatory nap time in which all children are required to lie on their beds without alternate activity permitted. There is currently limited evidence of the effects of such practices on children's napping patterns. This study examined the association between duration of mandatory nap times and group-level napping patterns in child care settings. Observations were undertaken in a community sample of 113 preschool rooms with a scheduled nap time (N = 2,114 children). Results showed that 83.5% of child care settings implemented a mandatory nap time (range = 15-145 min) while 14.2% provided alternate activities for children throughout the nap time period. Overall, 31% of children napped during nap times. Compared to rooms with ≤ 30 min of mandatory nap time, rooms with 31-60 min and > 60 min of mandatory nap time had a two-and-a-half and fourfold increase, respectively, in the proportion of children napping. Nap onset latency did not significantly differ across groups. Among preschool children, exposure to longer mandatory nap times in child care may increase incidence of napping.

Words to Sleep On: Naps Facilitate Verb Generalization in Habitually and Nonhabitually Napping Preschoolers

ERIC Educational Resources Information Center

Sandoval, Michelle; Leclerc, Julia A.; Gómez, Rebecca L.

2017-01-01

A nap soon after encoding leads to better learning in infancy. However, whether napping plays the same role in preschoolers' learning is unclear. In Experiment 1 (N = 39), 3-year-old habitual and nonhabitual nappers learned novel verbs before a nap or a period of wakefulness and received a generalization test examining word extension to novel…

MSX1 cooperates with histone H1b for inhibition of transcription and myogenesis.

PubMed

Lee, Hansol; Habas, Raymond; Abate-Shen, Cory

2004-06-11

During embryogenesis, differentiation of skeletal muscle is regulated by transcription factors that include members of the Msx homeoprotein family. By investigating Msx1 function in repression of myogenic gene expression, we identified a physical interaction between Msx1 and H1b, a specific isoform of mouse histone H1. We found that Msx1 and H1b bind to a key regulatory element of MyoD, a central regulator of skeletal muscle differentiation, where they induce repressed chromatin. Moreover, Msx1 and H1b cooperate to inhibit muscle differentiation in cell culture and in Xenopus animal caps. Our findings define a previously unknown function for "linker" histones in gene-specific transcriptional regulation.

Subjective and Objective Napping and Sleep in Older Adults: Are Evening Naps ‘Bad’ for Nighttime Sleep?

PubMed Central

Dautovich, Natalie D.; McCrae, Christina S.; Rowe, Meredeth

2014-01-01

Objectives To compare objective and subjective measurements of napping, and to examine the relationship between evening napping and nocturnal sleep in older adults. Design For twelve days, participants wore actigraphs and completed sleep diaries. Setting Community Participants 100 individuals who napped, 60–89 years (including good and poor sleepers with typical age-related medical comorbidities). Measurements Twelve days of sleep diary and actigraphy provided subjective and objective napping and sleep data. Results Evening naps (within 2 hours of bedtime) were characteristic of the sample with peak nap time occurring between 20:30–21:00 (average nap time occurred between 14:30–15:00). Two categories of nappers were identified: 1) day/evening – those who took both daytime and evening naps, and 2) daytime-only. Interestingly, no participants napped during the evening only. Day/evening nappers significantly underreported evening napping and demonstrated lower objectively measured sleep onset latencies (20 vs 26.5 minutes), less wake after sleep onset (51.4 vs 72.8 minutes), and higher sleep efficiencies (76.8 vs 82%) than daytime-only nappers. Conclusion Day/evening napping was prevalent amongst this sample of community-dwelling good/poor sleepers, but was not associated with impaired nocturnal sleep. Although the elimination or restriction of napping is a common element of cognitive-behavioral therapy for insomnia (CBTi), these results suggest that a uniform recommendation to restrict/eliminate napping (particularly evening napping) may not meet the needs of all older individuals with insomnia. PMID:18691289

Epigenetic regulation of planarian stem cells by the SET1/MLL family of histone methyltransferases.

PubMed

Hubert, Amy; Henderson, Jordana M; Ross, Kelly G; Cowles, Martis W; Torres, Jessica; Zayas, Ricardo M

2013-01-01

Chromatin regulation is a fundamental mechanism underlying stem cell pluripotency, differentiation, and the establishment of cell type-specific gene expression profiles. To examine the role of chromatin regulation in stem cells in vivo, we study regeneration in the freshwater planarian Schmidtea mediterranea. These animals possess a high concentration of pluripotent stem cells, which are capable of restoring any damaged or lost tissues after injury or amputation. Here, we identify the S. mediterranea homologs of the SET1/MLL family of histone methyltransferases and COMPASS and COMPASS-like complex proteins and investigate their role in stem cell function during regeneration. We identified six S. mediterranea homologs of the SET1/MLL family (set1, mll1/2, trr-1, trr-2, mll5-1 and mll5-2), characterized their patterns of expression in the animal, and examined their function by RNAi. All members of this family are expressed in the stem cell population and differentiated tissues. We show that set1, mll1/2, trr-1, and mll5-2 are required for regeneration and that set1, trr-1 and mll5-2 play roles in the regulation of mitosis. Most notably, knockdown of the planarian set1 homolog leads to stem cell depletion. A subset of planarian homologs of COMPASS and COMPASS-like complex proteins are also expressed in stem cells and implicated in regeneration, but the knockdown phenotypes suggest that some complex members also function in other aspects of planarian biology. This work characterizes the function of the SET1/MLL family in the context of planarian regeneration and provides insight into the role of these enzymes in adult stem cell regulation in vivo.

Identification of Peach NAP Transcription Factor Genes and Characterization of their Expression in Vegetative and Reproductive Organs during Development and Senescence

PubMed Central

Li, Fang; Li, Jinjin; Qian, Ming; Han, Mingyu; Cao, Lijun; Liu, Hangkong; Zhang, Dong; Zhao, Caiping

2016-01-01

The NAP (NAC-like, activated by AP3/P1) transcription factor belongs to a subfamily of the NAC transcription factor family, and is believed to have an important role in regulating plant growth and development. However, there is very little information about this subfamily in Rosaceous plants. We identified seven NAP genes in the peach genome. PpNAP2 was categorized in the NAP I group, and contained a conserved transcription activation region. The other PpNAP genes belonged to the NAP II group. The expression patterns of the PpNAP genes differed in various organs and developmental stages. PpNAP1 and PpNAP2 were highly expressed in mature and senescing flowers, but not in leaves, fruits, and flower buds. PpNAP3 and PpNAP5 were only expressed in leaves. The PpNAP4 expression level was high in mature and senescing fruits, while PpNAP6 and PpNAP7 expression was up-regulated in mature and senescent leaves and flowers. During the fruit development period, the PpNAP4 and PpNAP6 expression levels rapidly increased during the S1 and S4 stages, which suggests these genes are involved in the first exponential growth phase and fruit ripening. During the fruit ripening and softening period, the PpNAP1, PpNAP4, and PpNAP6 expression levels were high during the early storage period, which was accompanied by a rapid increase in ethylene production. PpNAP1, PpNAP4, and PpNAP6 expression slowly increased during the middle or late storage periods, and peaked at the end of the storage period. Additionally, abscisic acid (ABA)-treated fruits were softer and produced more ethylene than the controls. Furthermore, the PpNAP1, PpNAP4, and PpNAP6 expression levels were higher in ABA-treated fruits. These results suggest that PpNAP1, PpNAP4, and PpNAP6 are responsive to ABA and may regulate peach fruit ripening. PMID:26909092

Epigenetic regulation of planarian stem cells by the SET1/MLL family of histone methyltransferases

PubMed Central

Hubert, Amy; Henderson, Jordana M.; Ross, Kelly G.; Cowles, Martis W.; Torres, Jessica; Zayas, Ricardo M.

2013-01-01

Chromatin regulation is a fundamental mechanism underlying stem cell pluripotency, differentiation, and the establishment of cell type-specific gene expression profiles. To examine the role of chromatin regulation in stem cells in vivo, we study regeneration in the freshwater planarian Schmidtea mediterranea. These animals possess a high concentration of pluripotent stem cells, which are capable of restoring any damaged or lost tissues after injury or amputation. Here, we identify the S. mediterranea homologs of the SET1/MLL family of histone methyltransferases and COMPASS and COMPASS-like complex proteins and investigate their role in stem cell function during regeneration. We identified six S. mediterranea homologs of the SET1/MLL family (set1, mll1/2, trr-1, trr-2, mll5–1 and mll5–2), characterized their patterns of expression in the animal, and examined their function by RNAi. All members of this family are expressed in the stem cell population and differentiated tissues. We show that set1, mll1/2, trr-1, and mll5–2 are required for regeneration and that set1, trr-1 and mll5–2 play roles in the regulation of mitosis. Most notably, knockdown of the planarian set1 homolog leads to stem cell depletion. A subset of planarian homologs of COMPASS and COMPASS-like complex proteins are also expressed in stem cells and implicated in regeneration, but the knockdown phenotypes suggest that some complex members also function in other aspects of planarian biology. This work characterizes the function of the SET1/MLL family in the context of planarian regeneration and provides insight into the role of these enzymes in adult stem cell regulation in vivo. PMID:23235145

The napping behaviour of Australian university students.

PubMed

Lovato, Nicole; Lack, Leon; Wright, Helen

2014-01-01

The purpose of this study was to evaluate the self-reported sleep and napping behaviour of Australian university students and the relationship between napping and daytime functioning. A sample of 280 university first-year psychology students (median age  = 19.00 years) completed a 6-item napping behaviour questionnaire, a 12-item Daytime Feelings and Functioning Scale, the Pittsburg Sleep Quality Index and the Epworth Sleepiness Scale. Results indicated that 53.6% of students reported napping with 34% napping at least 1-2 times per week, and 17% napping three or more occasions per week. Long naps, those over 30 minutes, were taken by 77% of the napping students. Sixty-one percent of students reported they took long naps during the post-lunch dip period, from 2-4 pm. Students who nap at least once per week reported significantly more problems organizing their thoughts, gaining motivation, concentrating, and finishing tasks than students who did not nap. Students who napped also felt significantly more sleepy and depressed when compared to students who did not nap. The results also indicated that nap frequency increased with daytime sleepiness. The majority of students (51%) reported sleeping 6-7 hours per night or less. Overall, the results from this study suggest that among this population of Australian first-year university students habitual napping is common and may be used in an attempt to compensate for the detrimental effects of excessive sleepiness.

The Napping Behaviour of Australian University Students

PubMed Central

Lovato, Nicole; Lack, Leon; Wright, Helen

2014-01-01

The purpose of this study was to evaluate the self-reported sleep and napping behaviour of Australian university students and the relationship between napping and daytime functioning. A sample of 280 university first-year psychology students (median age  = 19.00 years) completed a 6-item napping behaviour questionnaire, a 12-item Daytime Feelings and Functioning Scale, the Pittsburg Sleep Quality Index and the Epworth Sleepiness Scale. Results indicated that 53.6% of students reported napping with 34% napping at least 1–2 times per week, and 17% napping three or more occasions per week. Long naps, those over 30 minutes, were taken by 77% of the napping students. Sixty-one percent of students reported they took long naps during the post-lunch dip period, from 2–4pm. Students who nap at least once per week reported significantly more problems organizing their thoughts, gaining motivation, concentrating, and finishing tasks than students who did not nap. Students who napped also felt significantly more sleepy and depressed when compared to students who did not nap. The results also indicated that nap frequency increased with daytime sleepiness. The majority of students (51%) reported sleeping 6–7 hours per night or less. Overall, the results from this study suggest that among this population of Australian first-year university students habitual napping is common and may be used in an attempt to compensate for the detrimental effects of excessive sleepiness. PMID:25412257

The COMPASS Family of Histone H3K4 Methylases: Mechanisms of Regulation in Development and Disease Pathogenesis

PubMed Central

Shilatifard, Ali

2014-01-01

The Saccharomyces cerevisiae Set1/COMPASS was the first histone H3 lysine 4 (H3K4) methylase identified over ten years ago. Since then, it has been demonstrated that Set1/COMPASS and its enzymatic product, H3K4 methylation, is highly conserved across the evolutionary tree. Although there is only one COMPASS in yeast, human cells bear at least six COMPASS family members each capable of methylating H3K4 with non-redundant functions. In yeast, the monoubiquitination of histone H2B by Rad6/Bre1 is required for proper H3K4 and H3K79 trimethylations. This histone crosstalk and its machinery are also highly conserved from yeast to human. In this review, the process of histone H2B monoubiquitination-dependent and independent histone H3K4 methylation as a mark of active transcription, enhancer signatures, and developmentally poised genes will be discussed. The misregulation of histone H2B monoubiquitination and H3K4 methylation results in the pathogenesis of human diseases including cancer. Recent findings in this regard will also be examined. PMID:22663077

Impact of the NAP-1 strain on disease severity, mortality, and recurrence of healthcare-associated Clostridium difficile infection.

PubMed

Bauer, Karri A; Johnston, Jessica E W; Wenzler, Eric; Goff, Debra A; Cook, Charles H; Balada-Llasat, Joan-Miquel; Pancholi, Preeti; Mangino, Julie E

2017-12-01

Studies are conflicting regarding the association of the North American pulsed-field gel electrophoresis type 1 (NAP1) strain in Clostridium difficile infection (CDI) and outcomes. We evaluated the association of NAP1 with healthcare-associated CDI disease severity, mortality, and recurrence at our academic medical center. Healthcare-associated CDI cases were identified from November 1, 2011 through January 31, 2013. Multivariable regression models were used to evaluate the associations of NAP1 with severe disease (based on the Hines VA severity score index), mortality, and recurrence. Among 5424 stool specimens submitted to the Clinical Microbiology Laboratory, 292 (5.4%) were positive for C. difficile by polymerase chain reaction (PCR) on or after hospital day 4; 70 (24%) of these specimens also tested positive for NAP1. During the study period, 247 (85%) patients had non-severe disease and 45 (15%) patients had severe disease. Among patients with non-severe disease, 65 (26%) had NAP1 and among patients with severe disease, 5 (11%) had NAP1. After controlling for potential confounders, NAP1 was not associated with an increased likelihood of severe disease (adjusted odds ratio [aOR] = 0.35; 95% confidence interval [CI], 0.13-0.93), in-hospital mortality (aOR = 1.02; 95% CI, 0.53-1.96), or recurrence (aOR = 1.16, 95% CI, 0.36-3.77). The NAP1 strain did not increase disease severity, mortality, or recurrence in this study, although the incidence of NAP1-positive healthcare associated-CDI was low. The role of strain typing in outcomes and treatment selection in patients with healthcare-associated CDI remains uncertain. Copyright © 2017 Elsevier Ltd. All rights reserved.

Herpes simplex virus type 1 tegument protein VP22 interacts with TAF-I proteins and inhibits nucleosome assembly but not regulation of histone acetylation by INHAT.

PubMed

van Leeuwen, Hans; Okuwaki, Mitsuru; Hong, Rui; Chakravarti, Debabrata; Nagata, Kyosuke; O'Hare, Peter

2003-09-01

Affinity chromatography was used to identify cellular proteins that interact with the herpes simplex virus (HSV) tegument protein VP22. Among a small set of proteins that bind specifically to VP22, we identified TAF-I (template-activating factor I), a chromatin remodelling protein and close homologue of the histone chaperone protein NAP-1. TAF-I has been shown previously to promote more ordered transfer of histones to naked DNA through a direct interaction with histones. TAF-I, as a subunit of the INHAT (inhibitor of acetyltransferases) protein complex, also binds to histones and masks them from being substrates for the acetyltransferases p300 and PCAF. Using in vitro assays for TAF-I activity in chromatin assembly, we show that VP22 inhibits nucleosome deposition on DNA by binding to TAF-I. We also observed that VP22 binds non-specifically to DNA, an activity that is abolished by TAF-I. However, the presence of VP22 does not affect the property of INHAT in inhibiting the histone acetyltransferase activity of p300 or PCAF in vitro. We speculate that this interaction could be relevant to HSV DNA organization early in infection, for example, by interfering with nucleosomal deposition on the genome. Consistent with this possibility was the observation that overexpression of TAF-I in transfected cells interferes with the progression of HSV-1 infection.

Association between Nighttime Sleep and Napping in Older Adults

PubMed Central

Goldman, Suzanne E.; Hall, Martica; Boudreau, Robert; Matthews, Karen A.; Cauley, Jane A.; Ancoli-Israel, Sonia; Stone, Katie L.; Rubin, Susan M.; Satterfield, Suzanne; Simonsick, Eleanor M.; Newman, Anne B.

2008-01-01

Study Objectives: Napping might indicate deficiencies in nighttime sleep, but the relationship is not well defined. We assessed the association of nighttime sleep duration and fragmentation with subsequent daytime sleep. Design: Cross-sectional study. Participants: 235 individuals (47.5% men, 29.7% black), age 80.1 (2.9) years. Measurements and Results: Nighttime and daytime sleep were measured with wrist actigraphy and sleep diaries for an average of 6.8 (SD 0.7) nights. Sleep parameters included total nighttime sleep (h), movement and fragmentation index (fragmentation), and total daytime sleep (h). The relationship of total nighttime sleep and fragmentation to napping (yes/no) was assessed using logistic regression. In individuals who napped, mixed random effects models were used to determine the association between the previous night sleep duration and fragmentation and nap duration, and nap duration and subsequent night sleep duration. All models were adjusted for age, race, gender, BMI, cognitive status, depression, cardiovascular disease, respiratory symptoms, diabetes, pain, fatigue, and sleep medication use. Naps were recorded in sleep diaries by 178 (75.7%) participants. The odds ratios (95% CI) for napping were higher for individuals with higher levels of nighttime fragmentation (2.1 [0.8, 5.7]), respiratory symptoms (2.4 [1.1, 5.4]), diabetes (6.1 [1.2, 30.7]), and pain (2.2 [1.0, 4.7]). Among nappers, neither sleep duration nor fragmentation the preceding night was associated with nap duration the next day. Conclusion: More sleep fragmentation was associated with higher odds of napping although not with nap duration. Further research is needed to determine the causal association between sleep fragmentation and daytime napping. Citation: Goldman SE; Hall M; Boudreau R; Matthews KA; Cauley JA; Ancoli-Israel S; Stone KL; Rubin SM; Satterfield S; Simonsick EM; Newman AB. Association between nighttime sleep and napping in older adults. SLEEP 2008

Expression of the histone chaperone SET/TAF-Iβ during the strobilation process of Mesocestoides corti (Platyhelminthes, Cestoda).

PubMed

Costa, Caroline B; Monteiro, Karina M; Teichmann, Aline; da Silva, Edileuza D; Lorenzatto, Karina R; Cancela, Martín; Paes, Jéssica A; Benitz, André de N D; Castillo, Estela; Margis, Rogério; Zaha, Arnaldo; Ferreira, Henrique B

2015-08-01

The histone chaperone SET/TAF-Iβ is implicated in processes of chromatin remodelling and gene expression regulation. It has been associated with the control of developmental processes, but little is known about its function in helminth parasites. In Mesocestoides corti, a partial cDNA sequence related to SET/TAF-Iβ was isolated in a screening for genes differentially expressed in larvae (tetrathyridia) and adult worms. Here, the full-length coding sequence of the M. corti SET/TAF-Iβ gene was analysed and the encoded protein (McSET/TAF) was compared with orthologous sequences, showing that McSET/TAF can be regarded as a SET/TAF-Iβ family member, with a typical nucleosome-assembly protein (NAP) domain and an acidic tail. The expression patterns of the McSET/TAF gene and protein were investigated during the strobilation process by RT-qPCR, using a set of five reference genes, and by immunoblot and immunofluorescence, using monospecific polyclonal antibodies. A gradual increase in McSET/TAF transcripts and McSET/TAF protein was observed upon development induction by trypsin, demonstrating McSET/TAF differential expression during strobilation. These results provided the first evidence for the involvement of a protein from the NAP family of epigenetic effectors in the regulation of cestode development.

Napping Characteristics and Restricted Participation in Valued Activities Among Older Adults.

PubMed

Owusu, Jocelynn T; Ramsey, Christine M; Tzuang, Marian; Kaufmann, Christopher N; Parisi, Jeanine M; Spira, Adam P

2018-03-02

Napping is associated with both positive and negative health outcomes among older adults. However, the association between particular napping characteristics (eg, frequency, duration, and whether naps were intentional) and daytime function is unclear. Participants were 2,739 community-dwelling Medicare beneficiaries aged ≥65 years from the nationally representative National Health and Aging Trends Study. Participants reported napping frequency, duration, and whether naps were intentional versus unintentional. Restricted participation in valued activities was measured by self-report. After adjusting for potential confounders and nighttime sleep duration, those who took intentional and unintentional naps had a greater odds of any valued activity restriction (ie, ≥1 valued activity restriction), compared to those who rarely/never napped (unintentional odds ratio [OR] = 1.34, 95% confidence interval [CI] 1.01, 1.79, intentional OR = 1.49, 95% CI 1.09, 2.04). There was no difference between unintentional napping and intentional napping with respect to any valued activity restriction after adjustment for demographics. Compared to participants napping "some days," those napping most days/every day had a greater odds of any valued activity restriction (OR = 1.68, 95% CI 1.30, 2.16). Moreover, each 30-minute increase in average nap duration was associated with a 25% greater odds of any valued activity restriction (OR = 1.25, 95% CI 1.10, 1.43). Older adults who took more frequent or longer naps were more likely to report activity restrictions, as were those who took intentional or unintentional naps. Additional longitudinal studies with objective measures of sleep are needed to further our understanding of associations between napping characteristics and daytime dysfunction. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Role of H1 Linker Histones in Mammalian Development and Stem Cell Differentiation

PubMed Central

Pan, Chenyi; Fan, Yuhong

2016-01-01

H1 linker histones are key chromatin architectural proteins facilitating the formation of higher order chromatin structures. The H1 family constitutes the most heterogeneous group of histone proteins, with eleven non-allelic H1 variants in mammals. H1 variants differ in their biochemical properties and exhibit significant sequence divergence from one another, yet most of them are highly conserved during evolution from mouse to human. H1 variants are differentially regulated during development and their cellular compositions undergo dramatic changes in embryogenesis, gametogenesis, tissue maturation and cellular differentiation. As a group, H1 histones are essential for mouse development and proper stem cell differentiation. Here we summarize our current knowledge on the expression and functions of H1 variants in mammalian development and stem cell differentiation. Their diversity, sequence conservation, complex expression and distinct functions suggest that H1s mediate chromatin reprogramming and contribute to the large variations and complexity of chromatin structure and gene expression in the mammalian genome. PMID:26689747

Histone H3 and the histone acetyltransferase Hat1p contribute to DNA double-strand break repair.

PubMed

Qin, Song; Parthun, Mark R

2002-12-01

The modification of newly synthesized histones H3 and H4 by type B histone acetyltransferases has been proposed to play a role in the process of chromatin assembly. The type B histone acetyltransferase Hat1p and specific lysine residues in the histone H3 NH(2)-terminal tail (primarily lysine 14) are redundantly required for telomeric silencing. As many gene products, including other factors involved in chromatin assembly, have been found to participate in both telomeric silencing and DNA damage repair, we tested whether mutations in HAT1 and the histone H3 tail were also sensitive to DNA-damaging agents. Indeed, mutations both in specific lysine residues in the histone H3 tail and in HAT1 resulted in sensitivity to methyl methanesulfonate. The DNA damage sensitivity of the histone H3 and HAT1 mutants was specific for DNA double-strand breaks, as these mutants were sensitive to the induction of an exogenous restriction endonuclease, EcoRI, but not to UV irradiation. While histone H3 mutations had minor effects on nonhomologous end joining, the primary defect in the histone H3 and HAT1 mutants was in the recombinational repair of DNA double-strand breaks. Epistasis analysis indicates that the histone H3 and HAT1 mutants may influence DNA double-strand break repair through Asf1p-dependent chromatin assembly.

Subjective and objective napping and sleep in older adults: are evening naps "bad" for nighttime sleep?

PubMed

Dautovich, Natalie D; McCrae, Christina S; Rowe, Meredeth

2008-09-01

To compare objective and subjective measurements of napping and to examine the relationship between evening napping and nocturnal sleep in older adults. For 12 days, participants wore actigraphs and completed sleep diaries. Community. One hundred individuals who napped, aged 60 to 89 (including good and poor sleepers with typical age-related medical comorbidities). Twelve days of sleep diary and actigraphy provided subjective and objective napping and sleep data. Evening naps (within 2 hours of bedtime) were characteristic of the sample, with peak nap time occurring between 20:30 and 21:00 (average nap time occurred between 14:30 and 15:00). Two categories of nappers were identified: those who took daytime and evening naps and daytime-only. No participants napped during the evening only. Day-and-evening nappers significantly underreported evening napping and demonstrated lower objectively measured sleep onset latencies (20.0 vs 26.5 minutes), less wake after sleep onset (51.4 vs 72.8 minutes), and higher sleep efficiencies (76.8 vs 82%) than daytime-only nappers. Day and evening napping was prevalent in this sample of community-dwelling good and poor sleepers but was not associated with impaired nocturnal sleep. Although the elimination or restriction of napping is a common element of cognitive-behavioral therapy for insomnia, these results suggest that a uniform recommendation to restrict or eliminate napping (particularly evening napping) may not meet the needs of all older individuals with insomnia.

Napping on the Night Shift: A Two-Hospital Implementation Project

PubMed Central

Brown, Jeanne Geiger; Sagherian, Knar; Zhu, Shijun; Wieroniey, Margaret; Blair, Lori; Warren, Joan; Hinds, Pamela; Szeles, Rose

2015-01-01

Some nurses who work the night shift experience high levels of sleepiness. Napping has been adopted as an effective countermeasure to sleepiness and fatigue in other safety-sensitive industries but has not had widespread acceptance in nursing. In this two-hospital implementation project, napping was offered to six nursing units where nurse executives had previously approved nap implementation for the night shift as a pilot project. Successful implementation occurred in only one of the six units with partial success in a second unit. Barriers primarily occurred at the point of seeking unit-based nursing leadership approval. On the successful unit, one hundred fifty three 30-minutes naps were taken during the 3-month pilot period. A Nap Experience Survey measured sleepiness prior to the nap, the nap duration and perceived sleep, sleep inertia after the nap, and the perceived helpfulness of the nap. A high level of sleepiness was present at the beginning of 44% of naps. For over half of naps, nurses reported sleeping slightly (43%) or deeply (14%). Sleep inertia was rare (very groggy or sluggish on arising, 1.3%). The average score of helpfulness of napping was high (7.3 on a 1–10 scale). Nurses who napped reported being less drowsy while driving home after their shift. These data suggest that when barriers to napping are overcome, napping on the nightshift is feasible and can reduce sleepiness and drowsy driving in nurses. PMID:27082421

Is daytime napping associated with inflammation in adolescents?

PubMed

Jakubowski, Karen P; Hall, Martica H; Marsland, Anna L; Matthews, Karen A

2016-12-01

Daytime napping has been associated with poor health outcomes in adults. It is not known whether daytime napping is similarly linked to adverse health in adolescents, although many report napping. The present study evaluated associations between daytime napping and 2 markers of increased inflammation, high-sensitivity C-reactive protein and interleukin-6 (IL-6), in healthy high school students. Two hundred thirty-four Black and White high school students completed a week of actigraph and diary measures of sleep and napping and provided a fasting blood sample. Napping measures were the proportion of days napped and the average minutes napped across 1 week during the school year. Linear regressions adjusted for age, sex, race, average nocturnal sleep duration, time between sleep protocol and blood draw, and body mass index percentile demonstrated that proportion of days napped measured by actigraphy, B(SE) = .41(.19), p < .05, across the full week was positively associated with IL-6. Higher proportions of school days napped between 2 p.m. and 6 p.m., B(SE) = .40(.20), p < .05, and between 6 p.m. and 10 p.m., B(SE) = .57(.28), p < .05, were associated with increased IL-6. No associations emerged between average actigraphy-assessed nap duration and either study outcome. Diary-reported napping was unrelated to either study outcome. Actigraphy-assessed napping and IL-6 are associated but the direction of the relationship remains to be determined. Overall, napping is an important factor to consider to better understand the relationship between short sleep and cardiovascular health in adolescents. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Comparison of Iron-Binding Ability Between Thr70-NapA and Ser70-NapA of Helicobacter pylori.

PubMed

Shan, Weiran; Kung, Hsiang-Fu; Ge, Ruiguang

2016-06-01

The neutrophil-activating protein (NapA) of Helicobacter pylori (H. pylori), with DNA-binding and iron seizing properties, is a fundamental virulence factor involved in H. pylori-related diseases. Compared with Ser70-NapA strain, Thr70-NapA strain is more intimately correlated with iron-deficiency anemia. To investigate whether two types of proteins differ in iron-binding ability, mutated Thr70-NapA and Ser70-NapA strains were established. Isothermal titration calorimetry (ITC) method was conducted to measure the binding between the NapA protein and Fe(2+) . The structural changes of NapA protein were also tested during iron interaction by fast protein liquid chromatography (FPLC) and circular dichroism (CD) methods. DNA-binding assay was performed for evaluate the affinity of both mutated and wild types of NapA with DNA. Mutated Thr70-NapA had higher iron-binding ability than wild Ser70-NapA. The structural stability of Thr70-NapA was disrupted and became more active along with the rising concentration of Fe(2+) , whereas no similar association was observed between Ser70-NapA and Fe(2+) level. When the iron/protein molar ratio ranged from 10 to 20, both Ser70-NapA and Thr70-NapA displayed weaker DNA-binding ability. Thr70-NapA has much stronger ability to sequester ferrous ion compared with Ser70-NapA in H. pylori. In addition, the DNA-binding property of NapA is dependent upon the Fe(2+) concentration. © 2015 John Wiley & Sons Ltd.

Napping in English preschool children and the association with parents' attitudes.

PubMed

Jones, Caroline Helen Dorothy; Ball, Helen Louise

2013-04-01

Age-independent variability in childrens' napping duration may be influenced by parental preference and attitudes and childrens' availability or lack of opportunity to nap. Our study examined English preschool childrens' napping duration, frequency and location, and the association of daily nap duration with parents' attitudes towards napping. Parents of three-year-old children in deprived and nondeprived areas of a town in North-East England were interviewed regarding their attitudes towards child napping and completed four-day and five night sleep diaries documenting their childrens' daytime and nighttime sleep. Of 84 children, half had at least one nap during the four-day study period (median [interquartile range] daily nap duration across all children was 1 [21] min; for nappers only was 21 [34] min). Naps tended to be infrequent and short and few (6%) occurred in a bedroom. Children whose parents allowed or encouraged napping had significantly longer daily nap duration (n=25, median [interquartile range] daily nap duration 21 [34] min) compared to those whose parents tried to prevent them from napping (n=29, 1 [21] min), and those whose parents reported that children did not want to nap (n=30, 0 [0] min) (U=23.21; p<.001). Positive parental attitude towards napping was associated with longer child nap duration. Napping appeared to be mainly sporadic and opportunistic and was negatively perceived and prevented by one-third of parents. The consequences of premature nap cessation are not known; given the importance of sufficient sleep in childhood, we should possibly consider enabling young children to nap more freely. Copyright © 2013 Elsevier B.V. All rights reserved.

HAC1 and HAF1 Histone Acetyltransferases Have Different Roles in UV-B Responses in Arabidopsis.

PubMed

Fina, Julieta P; Masotti, Fiorella; Rius, Sebastián P; Crevacuore, Franco; Casati, Paula

2017-01-01

Arabidopsis has 12 histone acetyltransferases grouped in four families: the GNAT/HAG, the MYST/HAM, the p300/CBP/HAC and the TAFII250/HAF families. We previously showed that ham1 and ham2 mutants accumulated higher damaged DNA after UV-B exposure than WT plants. In contrast, hag3 RNA interference transgenic plants showed less DNA damage and lower inhibition of plant growth by UV-B, and increased levels of UV-B-absorbing compounds. These results demonstrated that HAM1, HAM2, and HAG3 participate in UV-B-induced DNA damage repair and signaling. In this work, to further explore the role of histone acetylation in UV-B responses, a putative function of other acetyltransferases of the HAC and the HAF families was analyzed. Neither HAC nor HAF acetyltrasferases participate in DNA damage and repair after UV-B radiation in Arabidopsis. Despite this, haf1 mutants presented lower inhibition of leaf and root growth by UV-B, with altered expression of E2F transcription factors. On the other hand, hac1 plants showed a delay in flowering time after UV-B exposure and changes in FLC and SOC1 expression patterns. Our data indicate that HAC1 and HAF1 have crucial roles for in UV-B signaling, confirming that, directly or indirectly, both enzymes also have a role in UV-B responses.

HAC1 and HAF1 Histone Acetyltransferases Have Different Roles in UV-B Responses in Arabidopsis

PubMed Central

Fina, Julieta P.; Masotti, Fiorella; Rius, Sebastián P.; Crevacuore, Franco; Casati, Paula

2017-01-01

Arabidopsis has 12 histone acetyltransferases grouped in four families: the GNAT/HAG, the MYST/HAM, the p300/CBP/HAC and the TAFII250/HAF families. We previously showed that ham1 and ham2 mutants accumulated higher damaged DNA after UV-B exposure than WT plants. In contrast, hag3 RNA interference transgenic plants showed less DNA damage and lower inhibition of plant growth by UV-B, and increased levels of UV-B-absorbing compounds. These results demonstrated that HAM1, HAM2, and HAG3 participate in UV-B-induced DNA damage repair and signaling. In this work, to further explore the role of histone acetylation in UV-B responses, a putative function of other acetyltransferases of the HAC and the HAF families was analyzed. Neither HAC nor HAF acetyltrasferases participate in DNA damage and repair after UV-B radiation in Arabidopsis. Despite this, haf1 mutants presented lower inhibition of leaf and root growth by UV-B, with altered expression of E2F transcription factors. On the other hand, hac1 plants showed a delay in flowering time after UV-B exposure and changes in FLC and SOC1 expression patterns. Our data indicate that HAC1 and HAF1 have crucial roles for in UV-B signaling, confirming that, directly or indirectly, both enzymes also have a role in UV-B responses. PMID:28740501

Maternal Habitual Midday Napping Duration and Frequency are Associated with High Birthweight.

PubMed

Zheng, Xiaoxuan; Zhang, Lina; Shen, Lijun; Song, Lulu; Li, Hui; Liu, Bingqing; Li, Yuanyuan; Xia, Wei; Zhang, Bin; Xu, Shunqing; Wang, Youjie

2017-09-05

Habitual midday napping is a common habit in China, especially for pregnant women. The purpose of this study was to examine whether duration and frequency of maternal habitual midday napping were associated with high birthweight (HBW). A total of 10,482 participants from Healthy Baby Cohort were include in our analysis. The information of the mothers and their infants were abstracted from medical records, or obtained from questionnaire. Logistic regression models were used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of habitual midday napping duration and frequency with HBW. Of the participants, 8,705 (83.0%) reported having habitual midday napping. Duration and frequency of napping had a positive association with HBW without adjustment. After controlling for potential confounders, increasing risk of HBW was observed in participants who napped 1.5-2 hours (OR, 1.50, 95% CI, 1.14, 1.98), and ≥2 hours (OR, 1.35, 95% CI, 1.03, 1.78) compared with no habitual midday napping. Participants who took naps ≥5 days/week had a higher risk of HBW (OR, 1.37, 95% CI, 1.07, 1.77) compared with the women without naps. This suggests that longer (≥1.5 hours) and more frequent (≥5 days/week) maternal habitual midday napping were associated with an increased risk of HBW.

Histone Arginine Methylation

PubMed Central

Lorenzo, Alessandra Di; Bedford, Mark T.

2012-01-01

Arginine methylation is a common posttranslational modification (PTM). This type of PTM occurs on both nuclear and cytoplasmic proteins, and is particularly abundant on shuttling proteins. In this review, we will focus on one aspect of this PTM: the diverse roles that arginine methylation of the core histone tails play in regulating chromatin function. A family of nine protein arginine methyltransferases (PRMTs) catalyze methylation reactions, and a subset target histones. Importantly, arginine methylation of histone tails can promote or prevent the docking of key transcriptional effector molecules, thus playing a central role in the orchestration of the histone code. PMID:21074527

DNA-HMGB1 interaction: The nuclear aggregates of polyamine mediation.

PubMed

Iacomino, Giuseppe; Picariello, Gianluca; Sbrana, Francesca; Raiteri, Roberto; D'Agostino, Luciano

2016-10-01

Nuclear aggregates of polyamines (NAPs) are supramolecular compounds generated by the self-assembly of protonated nuclear polyamines (spermine, spermidine and putrescine) and phosphate ions. In the presence of genomic DNA, the hierarchical process of self-structuring ultimately produces nanotube-like polymers that envelop the double helix. Because of their modular nature and their aggregation-disaggregation dynamics, NAPs confer plasticity and flexibility to DNA. Through the disposition of charges, NAPs also enable a bidirectional stream of information between the genome and interacting moieties. High mobility group (HMG) B1 is a non-histone chromosomal protein that binds to DNA and that influences multiple nuclear processes. Because genomic DNA binds to either NAPs or HMGB1 protein, we explored the ability of in vitro self-assembled NAPs (ivNAPs) to mediate the DNA-HMGB1 interaction. To this end, we structured DNA-NAPs-HMGB1 and DNA-HMGB1-NAPs ternary complexes in vitro through opportune sequential incubations. Mobility shift electrophoresis and atomic force microscopy showed that the DNA-ivNAPs-HGMB1 complex had conformational assets supposedly more suitable those of the DNA-HGMB1-ivNAPs to comply with the physiological and functional requirements of DNA. Our findings indicated that ivNAPs act as mediators of the DNA-HMGB1 interaction. Copyright © 2016 Elsevier B.V. All rights reserved.

To Nap, Perchance to DREAM: A Factor Analysis of College Students' Self-Reported Reasons for Napping.

PubMed

Duggan, Katherine A; McDevitt, Elizabeth A; Whitehurst, Lauren N; Mednick, Sara C

2018-01-01

Although napping has received attention because of its associations with health and use as a method to understand the function of sleep, to our knowledge no study has systematically and statistically assessed reasons for napping. Using factor analysis, we determined the underlying structure of reasons for napping in diverse undergraduates (N = 430, 59% female) and examined their relationships with self-reported sleep, psychological health, and physical health. The five reasons for napping can be summarized using the acronym DREAM (Dysregulative, Restorative, Emotional, Appetitive, and Mindful). Only Emotional reasons for napping were uniformly related to lower well-being. The use of factor analysis raises possibilities for future research, including examining the stability, structure, and psychological and physical health processes related to napping throughout the lifespan.

To nap, perchance to DREAM: A factor analysis of college students’ self-reported reasons for napping

PubMed Central

Duggan, Katherine A.; McDevitt, Elizabeth A.; Whitehurst, Lauren N.; Mednick, Sara C.

2017-01-01

Although napping has received attention because of its associations with health and use as a method to understand the function of sleep, to our knowledge no study has systematically and statistically assessed reasons for napping. Using factor analysis, we determined the underlying structure of reasons for napping in diverse undergraduates (N=430, 59% female) and examined their relationships with self-reported sleep, psychological, and physical health. The 5 reasons for napping can be summarized using the acronym DREAM (Dysregulative, Restorative, Emotional, Appetitive, and Mindful). Only Emotional reasons for napping were uniformly related to lower well-being. The use of factor analysis raises possibilities for future research, including examining the stability, structure, and psychological and physical health processes related to napping throughout the lifespan. PMID:27347727

Germline-specific H1 variants: the "sexy" linker histones.

PubMed

Pérez-Montero, Salvador; Carbonell, Albert; Azorín, Fernando

2016-03-01

The eukaryotic genome is packed into chromatin, a nucleoprotein complex mainly formed by the interaction of DNA with the abundant basic histone proteins. The fundamental structural and functional subunit of chromatin is the nucleosome core particle, which is composed by 146 bp of DNA wrapped around an octameric protein complex formed by two copies of each core histone H2A, H2B, H3, and H4. In addition, although not an intrinsic component of the nucleosome core particle, linker histone H1 directly interacts with it in a monomeric form. Histone H1 binds nucleosomes near the exit/entry sites of linker DNA, determines nucleosome repeat length and stabilizes higher-order organization of nucleosomes into the ∼30 nm chromatin fiber. In comparison to core histones, histone H1 is less well conserved through evolution. Furthermore, histone H1 composition in metazoans is generally complex with most species containing multiple variants that play redundant as well as specific functions. In this regard, a characteristic feature is the presence of specific H1 variants that replace somatic H1s in the germline and during early embryogenesis. In this review, we summarize our current knowledge about their structural and functional properties.

A 30-Minute, but Not a 10-Minute Nighttime Nap is Associated with Sleep Inertia.

PubMed

Hilditch, Cassie J; Centofanti, Stephanie A; Dorrian, Jillian; Banks, Siobhan

2016-03-01

To assess sleep inertia following 10-min and 30-min naps during a simulated night shift. Thirty-one healthy adults (aged 21-35 y; 18 females) participated in a 3-day laboratory study that included one baseline (BL) sleep (22:00-07:00) and one experimental night involving randomization to either: total sleep deprivation (NO-NAP), a 10-min nap (10-NAP) or a 30-min nap (30-NAP). Nap opportunities ended at 04:00. A 3-min psychomotor vigilance task (PVT-B), digit-symbol substitution task (DSST), fatigue scale, sleepiness scale, and self-rated performance scale were undertaken pre-nap (03:00) and at 2, 17, 32, and 47 min post-nap. The 30-NAP (14.7 ± 5.7 min) had more slow wave sleep than the 10-NAP (0.8 ± 1.5 min; P < 0.001) condition. In the NO-NAP condition, PVT-B performance was worse than pre-nap (4.6 ± 0.3 1/sec) at 47 min post-nap (4.1 ± 0.4 1/sec; P < 0.001). There was no change across time in the 10-NAP condition. In the 30-NAP condition, performance immediately deteriorated from pre-nap (4.3 ± 0.3 1/sec) and was still worse at 47 min post-nap (4.0 ± 0.5 1/sec; P < 0.015). DSST performance deteriorated in the NO-NAP (worse than pre-nap from 17 to 47 min; P < 0.008), did not change in the 10-NAP, and was impaired 2 min post-nap in the 30-NAP condition (P = 0.028). All conditions self-rated performance as better than pre-nap for all post-nap test points (P < 0.001). This study is the first to show that a 10-min (but not a 30-min) nighttime nap had minimal sleep inertia and helped to mitigate short-term performance impairment during a simulated night shift. Self-rated performance did not reflect objective performance following a nap. © 2016 Associated Professional Sleep Societies, LLC.

Association between habitual daytime napping and metabolic syndrome: a population-based study.

PubMed

Lin, Diaozhu; Sun, Kan; Li, Feng; Qi, Yiqin; Ren, Meng; Huang, Chulin; Tang, Juying; Xue, Shengneng; Li, Yan; Yan, Li

2014-12-01

Our objective was to evaluate the association between habitual daytime napping and the prevalence of metabolic syndrome. We conducted a population-based study of 8,547 subjects aged 40 years or older. Metabolic syndrome was defined according to a harmonized definition from a joint statement and the recommended thresholds for the Chinese population. Information about sleep duration was self-reported. The prevalence of metabolic syndrome in the no daytime napping group, the 0 to 1 hour daytime napping group and the more than 1 hour daytime napping group were 35.0%, 36.0% and 44.5% among the females (P<0.0001). Increased daytime napping hours were positively associated with parameters of metabolic syndrome in the female subjects, including waist circumference, systolic blood pressure, triglycerides and fasting plasma glucose (P<0.05 for all). Multivariate adjusted logistic regression analysis revealed that, compared to the no habitual daytime napping females, napping for more than 1 hour was independently associated with an increased prevalence of metabolic syndrome (odds ratio 1.39, 95% confidence interval, 1.13-1.72). Compared to the female subjects in the no daytime napping group, those habitually napped for more than 1 hour exhibited 46% and 26% increases in the prevalence of central obesity and hypertriglyceridemia (all P<0.05). No statistically significant associations were detected between daytime napping hours and metabolic syndrome among the male subjects. Daytime napping is associated with an increased prevalence of metabolic syndrome in middle-aged non-obese Chinese women. Copyright © 2014. Published by Elsevier Inc.

Effects of histone acetylation and DNA methylation on p21( WAF1) regulation.

PubMed

Fang, Jing-Yuan; Lu, You-Yong

2002-06-01

Cell cycle progression is regulated by interactions between cyclins and cyclin-dependent kinases (CDKs). p21(WAF1) is one of the CIP/KIP family which inhibits CDKs activity. Increased expression of p21(WAF1) may play an important role in the growth arrest induced in transformed cells. Although the stability of the p21( WAF1) mRNA could be altered by different signals, cell differentiation and numerous influencing factors. However, recent studies suggest that two known mechanisms of epigenesis, i.e.gene inactivation by methylation in promoter region and changes to an inactive chromatin by histone deacetylation, seem to be the best candidate mechanisms for inactivation of p21( WAF1). To date, almost no coding region p21(WAF1) mutations have been found in tumor cells, despite extensive screening of hundreds of various tumors. Hypermethylation of the p21(WAF1) promoter region may represent an alternative mechanism by which the p21(WAF1/CIP1) gene can be inactivated. The reduction of cellular DNMT protein levels also induces a corresponding rapid increase in the cell cycle regulator p21(WAF1) protein demonstrating a regulatory link between DNMT and p21(WAF1) which is independent of methylation of DNA. Both histone hyperacetylation and hypoacetylation appear to be important in the carcinoma process, and induction of the p21(WAF1) gene by histone hyperacetylation may be a mechanism by which dietary fiber prevents carcinogenesis. Here, we review the influence of histone acetylation and DNA methylation on p21(WAF1) transcription, and affection of pathways or factors associated such as p 53, E2A, Sp1 as well as several histone deacetylation inhibitors.

Optimization of hydrothermal synthesis of pure phase zeolite Na-P1 from South African coal fly ashes.

PubMed

Musyoka, Nicholas M; Petrik, Leslie F; Gitari, Wilson M; Balfour, Gillian; Hums, Eric

2012-01-01

This study was aimed at optimizing the synthesis conditions for pure phase zeolite Na-P1 from three coal fly ashes obtained from power stations in the Mpumalanga province of South Africa. Synthesis variables evaluated were: hydrothermal treatment time (12-48 hours), temperature (100-160°C) and varying molar quantities of water during the hydrothermal treatment step (H(2)O:SiO(2) molar ratio ranged between 0-0.49). The optimum synthesis conditions for preparing pure phase zeolite Na-P1 were achieved when the molar regime was 1 SiO(2): 0.36 Al(2)O(3): 0.59 NaOH: 0.49 H(2)O and ageing was done at 47°C for 48 hours. The optimum hydrothermal treatment time and temperature was 48 hours and 140°C, respectively. Fly ashes sourced from two coal-fired power plants (A, B) were found to produce nearly same high purity zeolite Na-P1 under identical conditions whereas the third fly ash (C) lead to a low quality zeolite Na-P1 under these conditions. The cation exchange capacity for the high pure phase was found to be 4.11 meq/g. These results highlight the fact that adjustment of reactant composition and presynthesis or synthesis parameters, improved quality of zeolite Na-P1 can be achieved and hence an improved potential for application of zeolites prepared from coal fly ash.

A 30-Minute, but Not a 10-Minute Nighttime Nap is Associated with Sleep Inertia

PubMed Central

Hilditch, Cassie J.; Centofanti, Stephanie A.; Dorrian, Jillian; Banks, Siobhan

2016-01-01

Study Objectives: To assess sleep inertia following 10-min and 30-min naps during a simulated night shift. Methods: Thirty-one healthy adults (aged 21–35 y; 18 females) participated in a 3-day laboratory study that included one baseline (BL) sleep (22:00–07:00) and one experimental night involving randomization to either: total sleep deprivation (NO-NAP), a 10-min nap (10-NAP) or a 30-min nap (30-NAP). Nap opportunities ended at 04:00. A 3-min psychomotor vigilance task (PVT-B), digit-symbol substitution task (DSST), fatigue scale, sleepiness scale, and self-rated performance scale were undertaken pre-nap (03:00) and at 2, 17, 32, and 47 min post-nap. Results: The 30-NAP (14.7 ± 5.7 min) had more slow wave sleep than the 10-NAP (0.8 ± 1.5 min; P < 0.001) condition. In the NO-NAP condition, PVT-B performance was worse than pre-nap (4.6 ± 0.3 1/sec) at 47 min post-nap (4.1 ± 0.4 1/sec; P < 0.001). There was no change across time in the 10-NAP condition. In the 30-NAP condition, performance immediately deteriorated from pre-nap (4.3 ± 0.3 1/sec) and was still worse at 47 min post-nap (4.0 ± 0.5 1/sec; P < 0.015). DSST performance deteriorated in the NO-NAP (worse than pre-nap from 17 to 47 min; P < 0.008), did not change in the 10-NAP, and was impaired 2 min post-nap in the 30-NAP condition (P = 0.028). All conditions self-rated performance as better than pre-nap for all post-nap test points (P < 0.001). Conclusions: This study is the first to show that a 10-min (but not a 30-min) nighttime nap had minimal sleep inertia and helped to mitigate short-term performance impairment during a simulated night shift. Self-rated performance did not reflect objective performance following a nap. Citation: Hilditch CJ, Centofanti SA, Dorrian J, Banks S. A 30-minute, but not a 10-minute nighttime nap is associated with sleep inertia. SLEEP 2016;39(3):675–685. PMID:26715234

Epigenetic control of alternative mRNA processing at the imprinted Herc3/Nap1l5 locus

PubMed Central

Cowley, Michael; Wood, Andrew J.; Böhm, Sabrina; Schulz, Reiner; Oakey, Rebecca J.

2012-01-01

Alternative polyadenylation increases transcriptome diversity by generating multiple transcript isoforms from a single gene. It is thought that this process can be subject to epigenetic regulation, but few specific examples of this have been reported. We previously showed that the Mcts2/H13 locus is subject to genomic imprinting and that alternative polyadenylation of H13 transcripts occurs in an allele-specific manner, regulated by epigenetic mechanisms. Here, we demonstrate that allele-specific polyadenylation occurs at another imprinted locus with similar features. Nap1l5 is a retrogene expressed from the paternally inherited allele, is situated within an intron of a ‘host’ gene Herc3, and overlaps a CpG island that is differentially methylated between the parental alleles. In mouse brain, internal Herc3 polyadenylation sites upstream of Nap1l5 are used on the paternally derived chromosome, from which Nap1l5 is expressed, whereas a downstream site is used more frequently on the maternally derived chromosome. Ablating DNA methylation on the maternal allele at the Nap1l5 promoter increases the use of an internal Herc3 polyadenylation site and alters exon splicing. These changes demonstrate the influence of epigenetic mechanisms in regulating Herc3 alternative mRNA processing. Internal Herc3 polyadenylation correlates with expression levels of Nap1l5, suggesting a possible role for transcriptional interference. Similar mechanisms may regulate alternative polyadenylation elsewhere in the genome. PMID:22790983

Chromatin signaling to kinetochores: Trans-regulation of Dam1 methylation by histone H2B ubiquitination

PubMed Central

Latham, John A.; Chosed, Renée J.; Wang, Shanzhi; Dent, Sharon Y.R.

2011-01-01

Summary Histone H3K4 trimethylation by the Set1/MLL family of proteins provides a hallmark for transcriptional activity from yeast to humans. In S. cerevisiae, H3K4 methylation is mediated by the Set1-containing COMPASS complex and is regulated in trans by prior ubiquitination of histone H2BK123. All of the events that regulate H2BK123ub and H3K4me are thought to occur at gene promoters. Here we report that this pathway is indispensable for methylation of the only other known substrate of Set1, K233 in Dam1, at kinetochores. Deletion of RAD6, BRE1, or Paf1 complex members abolishes Dam1 methylation, as does mutation of H2BK123. Our results demonstrate that Set1-mediated methylation is regulated by a general pathway regardless of substrate that is composed of transcriptional regulatory factors functioning independently of transcription. Moreover, our data identify a node of regulatory cross-talk in trans between a histone modification and modification on a non-histone protein, demonstrating that changing chromatin states can signal functional changes in other essential cellular proteins and machineries. PMID:21884933

Histone HIST1H1C/H1.2 regulates autophagy in the development of diabetic retinopathy.

PubMed

Wang, Wenjun; Wang, Qing; Wan, Danyang; Sun, Yue; Wang, Lin; Chen, Hong; Liu, Chengyu; Petersen, Robert B; Li, Jianshuang; Xue, Weili; Zheng, Ling; Huang, Kun

2017-05-04

Autophagy plays critical and complex roles in many human diseases, including diabetes and its complications. However, the role of autophagy in the development of diabetic retinopathy remains uncertain. Core histone modifications have been reported involved in the development of diabetic retinopathy, but little is known about the histone variants. Here, we observed increased autophagy and histone HIST1H1C/H1.2, an important variant of the linker histone H1, in the retinas of type 1 diabetic rodents. Overexpression of histone HIST1H1C upregulates SIRT1 and HDAC1 to maintain the deacetylation status of H4K16, leads to upregulation of ATG proteins, then promotes autophagy in cultured retinal cell line. Histone HIST1H1C overexpression also promotes inflammation and cell toxicity in vitro. Knockdown of histone HIST1H1C reduces both the basal and stresses (including high glucose)-induced autophagy, and inhibits high glucose induced inflammation and cell toxicity. Importantly, AAV-mediated histone HIST1H1C overexpression in the retinas leads to increased autophagy, inflammation, glial activation and neuron loss, similar to the pathological changes identified in the early stage of diabetic retinopathy. Furthermore, knockdown of histone Hist1h1c by siRNA in the retinas of diabetic mice significantly attenuated the diabetes-induced autophagy, inflammation, glial activation and neuron loss. These results indicate that histone HIST1H1C may offer a novel therapeutic target for preventing diabetic retinopathy.

Nitric Oxide Modulates Histone Acetylation at Stress Genes by Inhibition of Histone Deacetylases1[OPEN

PubMed Central

Mengel, Alexander; Ageeva, Alexandra; Durner, Jörg

2017-01-01

Histone acetylation, which is an important mechanism to regulate gene expression, is controlled by the opposing action of histone acetyltransferases and histone deacetylases (HDACs). In animals, several HDACs are subjected to regulation by nitric oxide (NO); in plants, however, it is unknown whether NO affects histone acetylation. We found that treatment with the physiological NO donor S-nitrosoglutathione (GSNO) increased the abundance of several histone acetylation marks in Arabidopsis (Arabidopsis thaliana), which was strongly diminished in the presence of the NO scavenger 2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide. This increase was likely triggered by NO-dependent inhibition of HDAC activity, since GSNO and S-nitroso-N-acetyl-dl-penicillamine significantly and reversibly reduced total HDAC activity in vitro (in nuclear extracts) and in vivo (in protoplasts). Next, genome-wide H3K9/14ac profiles in Arabidopsis seedlings were generated by chromatin immunoprecipitation sequencing, and changes induced by GSNO, GSNO/2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide or trichostatin A (an HDAC inhibitor) were quantified, thereby identifying genes that display putative NO-regulated histone acetylation. Functional classification of these genes revealed that many of them are involved in the plant defense response and the abiotic stress response. Furthermore, salicylic acid, which is the major plant defense hormone against biotrophic pathogens, inhibited HDAC activity and increased histone acetylation by inducing endogenous NO production. These data suggest that NO affects histone acetylation by targeting and inhibiting HDAC complexes, resulting in the hyperacetylation of specific genes. This mechanism might operate in the plant stress response by facilitating the stress-induced transcription of genes. PMID:27980017

Replication-Independent Histone Deposition by the HIR Complex and Asf1

PubMed Central

Green, Erin M.; Antczak, Andrew J.; Bailey, Aaron O.; Franco, Alexa A.; Wu, Kevin J.; Yates, John R.; Kaufman, Paul D.

2010-01-01

Summary The orderly deposition of histones onto DNA is mediated by conserved assembly complexes, including Chromatin Assembly Factor-1 (CAF-1) and the Hir proteins [1–4]. CAF-1 and the Hir proteins operate in distinct but functionally overlapping histone deposition pathways in vivo [5, 6]. The Hir proteins and CAF-1 share a common partner, the highly conserved histone H3/H4-binding protein Asf1, which binds the middle subunit of CAF-1 as well as to Hir proteins [7–11]. Asf1 binds to newly synthesized histones H3/H4 [12] and this complex stimulates histone deposition by CAF-1 [7, 12, 13]. In yeast, Asf1 is required for the contribution of the Hir proteins to gene silencing [7, 14]. Here, we demonstrate that Hir1, Hir2, Hir3 and Hpc2 comprise the HIR complex, which co-purifies with histone deposition protein Asf1. Together, the HIR complex and Asf1 deposit histones onto DNA in a replication-independent manner. Histone deposition by the HIR complex and Asf1 is impaired by a mutation in Asf1 that inhibits HIR binding. These data indicate that the HIR complex and Asf1 proteins function together as a conserved eukaryotic pathway for histone replacement throughout the cell cycle. PMID:16303565

Naps Enhance Executive Attention in Preschool-Aged Children.

PubMed

Cremone, Amanda; McDermott, Jennifer M; Spencer, Rebecca M C

2017-09-01

Executive attention is impaired following sleep loss in school-aged children, adolescents, and adults. Whether naps improve attention relative to nap deprivation in preschool-aged children is unknown. The aim of this study was to compare executive attention in preschool children following a nap and an interval of wake. Sixty-nine children, 35-70 months of age, completed a Flanker task to assess executive attention following a nap and an equivalent interval of wake. Overall, accuracy was greater after the nap compared with the wake interval. Reaction time(s) did not differ between the nap and wake intervals. Results did not differ between children who napped consistently and those who napped inconsistently, suggesting that naps benefit executive attention of preschoolers regardless of nap habituality. These results indicate that naps enhance attention in preschool children. As executive attention supports executive functioning and learning, nap promotion may improve early education outcomes. © The Author 2017. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Structural insights into the regulation and the recognition of histone marks by the SET domain of NSD1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morishita, Masayo; Di Luccio, Eric, E-mail: eric.diluccio@gmail.com

2011-08-26

Highlights: {yields} NSD1, NSD2/MMSET/WHSC1, and NSD3/WHSC1L1 are histone methyltransferases linked to numerous cancers. {yields} Little is known about the NSD pathways and HMTase inhibitors are sorely needed in the epigenetic therapy of cancers. {yields} We investigate the regulation and the recognition of histone marks by the SET domain of NSD1. {yields} A unique and key mechanism is driven by a loop at the interface of the SET and postSET region. {yields} Implications for developing specific and selective HMTase inhibitors are presented. -- Abstract: The development of epigenetic therapies fuels cancer hope. DNA-methylation inhibitors, histone-deacetylase and histone-methyltransferase (HMTase) inhibitors are beingmore » developed as the utilization of epigenetic targets is emerging as an effective and valuable approach to chemotherapy as well as chemoprevention of cancer. The nuclear receptor binding SET domain (NSD) protein is a family of three HMTases, NSD1, NSD2/MMSET/WHSC1, and NSD3/WHSC1L1 that are critical in maintaining the chromatin integrity. A growing number of studies have reported alterations or amplifications of NSD1, NSD2, or NSD3 in numerous carcinogenic events. Reducing NSDs activity through specific lysine-HMTase inhibitors appears promising to help suppressing cancer growth. However, little is known about the NSD pathways and our understanding of the histone lysine-HMTase mechanism is partial. To shed some light on both the recognition and the regulation of epigenetic marks by the SET domain of the NSD family, we investigate the structural mechanisms of the docking of the histone-H4 tail on the SET domain of NSD1. Our finding exposes a key regulatory and recognition mechanism driven by the flexibility of a loop at the interface of the SET and postSET region. Finally, we prospect the special value of this regulatory region for developing specific and selective NSD inhibitors for the epigenetic therapy of cancers.« less

C-NAP1 and rootletin restrain DNA damage-induced centriole splitting and facilitate ciliogenesis.

PubMed

Conroy, Pauline C; Saladino, Chiara; Dantas, Tiago J; Lalor, Pierce; Dockery, Peter; Morrison, Ciaran G

2012-10-15

Cilia are found on most human cells and exist as motile cilia or non-motile primary cilia. Primary cilia play sensory roles in transducing various extracellular signals, and defective ciliary functions are involved in a wide range of human diseases. Centrosomes are the principal microtubule-organizing centers of animal cells and contain two centrioles. We observed that DNA damage causes centriole splitting in non-transformed human cells, with isolated centrioles carrying the mother centriole markers CEP170 and ninein but not kizuna or cenexin. Loss of centriole cohesion through siRNA depletion of C-NAP1 or rootletin increased radiation-induced centriole splitting, with C-NAP1-depleted isolated centrioles losing mother markers. As the mother centriole forms the basal body in primary cilia, we tested whether centriole splitting affected ciliogenesis. While irradiated cells formed apparently normal primary cilia, most cilia arose from centriolar clusters, not from isolated centrioles. Furthermore, C-NAP1 or rootletin knockdown reduced primary cilium formation. Therefore, the centriole cohesion apparatus at the proximal end of centrioles may provide a target that can affect primary cilium formation as part of the DNA damage response.

Structural and Histone Binding Ability Characterizations of Human PWWP Domains

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Hong; Zeng, Hong; Lam, Robert

2013-09-25

The PWWP domain was first identified as a structural motif of 100-130 amino acids in the WHSC1 protein and predicted to be a protein-protein interaction domain. It belongs to the Tudor domain 'Royal Family', which consists of Tudor, chromodomain, MBT and PWWP domains. While Tudor, chromodomain and MBT domains have long been known to bind methylated histones, PWWP was shown to exhibit histone binding ability only until recently. The PWWP domain has been shown to be a DNA binding domain, but sequence analysis and previous structural studies show that the PWWP domain exhibits significant similarity to other 'Royal Family' members,more » implying that the PWWP domain has the potential to bind histones. In order to further explore the function of the PWWP domain, we used the protein family approach to determine the crystal structures of the PWWP domains from seven different human proteins. Our fluorescence polarization binding studies show that PWWP domains have weak histone binding ability, which is also confirmed by our NMR titration experiments. Furthermore, we determined the crystal structures of the BRPF1 PWWP domain in complex with H3K36me3, and HDGF2 PWWP domain in complex with H3K79me3 and H4K20me3. PWWP proteins constitute a new family of methyl lysine histone binders. The PWWP domain consists of three motifs: a canonical {beta}-barrel core, an insertion motif between the second and third {beta}-strands and a C-terminal {alpha}-helix bundle. Both the canonical {beta}-barrel core and the insertion motif are directly involved in histone binding. The PWWP domain has been previously shown to be a DNA binding domain. Therefore, the PWWP domain exhibits dual functions: binding both DNA and methyllysine histones.« less

Structural Basis for the Histone Chaperone Activity of Asf1

PubMed Central

English, Christine M.; Adkins, Melissa W.; Carson, Joshua J.; Churchill, Mair E.A.; Tyler, Jessica K.

2010-01-01

SUMMARY Asf1 is a highly conserved chaperone of histones H3/H4 that assembles or disassembles chromatin during transcription, replication, and repair. The structure of the globular domain of Asf1 bound to H3/H4 determined by X-ray crystallography to a resolution of 1.7 Å shows how Asf1 binds the H3/H4 heterodimer, enveloping the C-terminus of histone H3 and physically blocking formation of the H3/H4 heterotetramer. Unexpectedly, the C-terminus of histone H4 that forms a mini-beta sheet with histone H2A in the nucleosome, undergoes a major conformational change upon binding to Asf1 and adds a beta strand to the Asf1 beta-sheet sandwich. Interactions with both H3 and H4 were required for Asf1 histone chaperone function in vivo and in vitro. The Asf1-H3/H4 structure suggests a “strand-capture” mechanism whereby the H4 tail acts as a lever to facilitate chromatin disassembly / assembly that may be used ubiquitously by histone chaperones. PMID:17081973

Is Daytime Napping Associated With Inflammation In Adolescents?

PubMed Central

Jakubowski, Karen P.; Hall, Martica H.; Marsland, Anna L.; Matthews, Karen A.

2016-01-01

Objective Daytime napping has been associated with poor health outcomes in adults. It is not known whether daytime napping is similarly linked to adverse health in adolescents, although many report napping. The present study evaluated associations between daytime napping and two markers of increased inflammation, high sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6), in healthy high school students. Methods 234 black and white high school students completed a week of actigraph and diary measures of sleep and napping and provided a fasting blood sample. Napping measures were the proportion of days napped and the average minutes napped across one week during the school year. Results Linear regressions adjusted for age, sex, race, average nocturnal sleep duration, time between sleep protocol and blood draw, and BMI percentile demonstrated that proportion of days napped measured by actigraphy [B(SE)=.41(.19), p<.05] across the full week was positively associated with IL-6. Higher proportions of school days napped between 2 p.m. and 6 p.m. [B(SE)=.40(.20), p<.05] and between 6 p.m. and 10 p.m. [B(SE)=.57(.28), p<.05] were associated with increased IL-6. No associations emerged between average actigraphy-assessed nap duration and either study outcome. Diary-reported napping was unrelated to either study outcome. Conclusions Actigraphy-assessed napping and IL-6 are associated but the direction of the relationship remains to be determined. Overall, napping is an important factor to consider in order to better understand the relationship between short sleep and cardiovascular health in adolescents. PMID:27253429

Genome-wide identification of sweet orange (Citrus sinensis) histone modification gene families and their expression analysis during the fruit development and fruit-blue mold infection process

PubMed Central

Xu, Jidi; Xu, Haidan; Liu, Yuanlong; Wang, Xia; Xu, Qiang; Deng, Xiuxin

2015-01-01

In eukaryotes, histone acetylation and methylation have been known to be involved in regulating diverse developmental processes and plant defense. These histone modification events are controlled by a series of histone modification gene families. To date, there is no study regarding genome-wide characterization of histone modification related genes in citrus species. Based on the two recent sequenced sweet orange genome databases, a total of 136 CsHMs (Citrus sinensis histone modification genes), including 47 CsHMTs (histone methyltransferase genes), 23 CsHDMs (histone demethylase genes), 50 CsHATs (histone acetyltransferase genes), and 16 CsHDACs (histone deacetylase genes) were identified. These genes were categorized to 11 gene families. A comprehensive analysis of these 11 gene families was performed with chromosome locations, phylogenetic comparison, gene structures, and conserved domain compositions of proteins. In order to gain an insight into the potential roles of these genes in citrus fruit development, 42 CsHMs with high mRNA abundance in fruit tissues were selected to further analyze their expression profiles at six stages of fruit development. Interestingly, a numbers of genes were expressed highly in flesh of ripening fruit and some of them showed the increasing expression levels along with the fruit development. Furthermore, we analyzed the expression patterns of all 136 CsHMs response to the infection of blue mold (Penicillium digitatum), which is the most devastating pathogen in citrus post-harvest process. The results indicated that 20 of them showed the strong alterations of their expression levels during the fruit-pathogen infection. In conclusion, this study presents a comprehensive analysis of the histone modification gene families in sweet orange and further elucidates their behaviors during the fruit development and the blue mold infection responses. PMID:26300904

Genome-wide identification of sweet orange (Citrus sinensis) histone modification gene families and their expression analysis during the fruit development and fruit-blue mold infection process.

PubMed

Xu, Jidi; Xu, Haidan; Liu, Yuanlong; Wang, Xia; Xu, Qiang; Deng, Xiuxin

2015-01-01

In eukaryotes, histone acetylation and methylation have been known to be involved in regulating diverse developmental processes and plant defense. These histone modification events are controlled by a series of histone modification gene families. To date, there is no study regarding genome-wide characterization of histone modification related genes in citrus species. Based on the two recent sequenced sweet orange genome databases, a total of 136 CsHMs (Citrus sinensis histone modification genes), including 47 CsHMTs (histone methyltransferase genes), 23 CsHDMs (histone demethylase genes), 50 CsHATs (histone acetyltransferase genes), and 16 CsHDACs (histone deacetylase genes) were identified. These genes were categorized to 11 gene families. A comprehensive analysis of these 11 gene families was performed with chromosome locations, phylogenetic comparison, gene structures, and conserved domain compositions of proteins. In order to gain an insight into the potential roles of these genes in citrus fruit development, 42 CsHMs with high mRNA abundance in fruit tissues were selected to further analyze their expression profiles at six stages of fruit development. Interestingly, a numbers of genes were expressed highly in flesh of ripening fruit and some of them showed the increasing expression levels along with the fruit development. Furthermore, we analyzed the expression patterns of all 136 CsHMs response to the infection of blue mold (Penicillium digitatum), which is the most devastating pathogen in citrus post-harvest process. The results indicated that 20 of them showed the strong alterations of their expression levels during the fruit-pathogen infection. In conclusion, this study presents a comprehensive analysis of the histone modification gene families in sweet orange and further elucidates their behaviors during the fruit development and the blue mold infection responses.

The Histone Database: an integrated resource for histones and histone fold-containing proteins

PubMed Central

Mariño-Ramírez, Leonardo; Levine, Kevin M.; Morales, Mario; Zhang, Suiyuan; Moreland, R. Travis; Baxevanis, Andreas D.; Landsman, David

2011-01-01

Eukaryotic chromatin is composed of DNA and protein components—core histones—that act to compactly pack the DNA into nucleosomes, the fundamental building blocks of chromatin. These nucleosomes are connected to adjacent nucleosomes by linker histones. Nucleosomes are highly dynamic and, through various core histone post-translational modifications and incorporation of diverse histone variants, can serve as epigenetic marks to control processes such as gene expression and recombination. The Histone Sequence Database is a curated collection of sequences and structures of histones and non-histone proteins containing histone folds, assembled from major public databases. Here, we report a substantial increase in the number of sequences and taxonomic coverage for histone and histone fold-containing proteins available in the database. Additionally, the database now contains an expanded dataset that includes archaeal histone sequences. The database also provides comprehensive multiple sequence alignments for each of the four core histones (H2A, H2B, H3 and H4), the linker histones (H1/H5) and the archaeal histones. The database also includes current information on solved histone fold-containing structures. The Histone Sequence Database is an inclusive resource for the analysis of chromatin structure and function focused on histones and histone fold-containing proteins. Database URL: The Histone Sequence Database is freely available and can be accessed at http://research.nhgri.nih.gov/histones/. PMID:22025671

Plant homologs of mammalian MBT-domain protein-regulated KDM1 histone lysine demethylases do not interact with plant Tudor/PWWP/MBT-domain proteins

PubMed Central

Sadiq, Irfan; Keren, Ido; Citovsky, Vitaly

2016-01-01

Histone lysine demethylases of the LSD1/KDM1 family play important roles in epigenetic regulation of eukaryotic chromatin, and they are conserved between plants and animals. Mammalian LSD1 is thought to be targeted to its substrates, i.e., methylated histones, by an MBT-domain protein SFMBT1 that represents a component of the LSD1-based repressor complex and binds methylated histones. Because MBT-domain proteins are conserved between different organisms, from animals to plants, we examined whether the KDM1-type histone lysine demethylases KDM1C and FLD of Arabidopsis interact with the Arabidopsis Tudor/PWWP/MBT-domain SFMBT1-like proteins SL1, SL2, SL3, and SL4. No such interaction was detected using the bimolecular fluorescence complementation assay in living plant cells. Thus, plants most likely direct their KDM1 chromatin-modifying enzymes to methylated histones of the target chromatin by a mechanism different from that employed by the mammalian cells. PMID:26826387

Plant homologs of mammalian MBT-domain protein-regulated KDM1 histone lysine demethylases do not interact with plant Tudor/PWWP/MBT-domain proteins.

PubMed

Sadiq, Irfan; Keren, Ido; Citovsky, Vitaly

2016-02-19

Histone lysine demethylases of the LSD1/KDM1 family play important roles in epigenetic regulation of eukaryotic chromatin, and they are conserved between plants and animals. Mammalian LSD1 is thought to be targeted to its substrates, i.e., methylated histones, by an MBT-domain protein SFMBT1 that represents a component of the LSD1-based repressor complex and binds methylated histones. Because MBT-domain proteins are conserved between different organisms, from animals to plants, we examined whether the KDM1-type histone lysine demethylases KDM1C and FLD of Arabidopsis interact with the Arabidopsis Tudor/PWWP/MBT-domain SFMBT1-like proteins SL1, SL2, SL3, and SL4. No such interaction was detected using the bimolecular fluorescence complementation assay in living plant cells. Thus, plants most likely direct their KDM1 chromatin-modifying enzymes to methylated histones of the target chromatin by a mechanism different from that employed by the mammalian cells. Copyright © 2016 Elsevier Inc. All rights reserved.

Improving alertness and performance in emergency department physicians and nurses: the use of planned naps.

PubMed

Smith-Coggins, Rebecca; Howard, Steven K; Mac, Dat T; Wang, Cynthia; Kwan, Sharon; Rosekind, Mark R; Sowb, Yasser; Balise, Raymond; Levis, Joel; Gaba, David M

2006-11-01

We examine whether a 40-minute nap opportunity at 3 AM can improve cognitive and psychomotor performance in physicians and nurses working 12-hour night shifts. This is a randomized controlled trial of 49 physicians and nurses working 3 consecutive night shifts in an academic emergency department. Subjects were randomized to a control group (no-nap condition=NONE) or nap intervention group (40-minute nap opportunity at 3 AM=NAP). The main outcome measures were Psychomotor Vigilance Task, Probe Recall Memory Task, CathSim intravenous insertion virtual reality simulation, and Profile of Mood States, which were administered before (6:30 PM), during (4 AM), and after (7:30 AM) night shifts. A 40-minute driving simulation was administered at 8 AM and videotaped for behavioral signs of sleepiness and driving accuracy. During the nap period, standard polysomnographic data were recorded. Polysomnographic data revealed that 90% of nap subjects were able to sleep for an average of 24.8 minutes (SD 11.1). At 7:30 AM, the nap group had fewer performance lapses (NAP 3.13, NONE 4.12; p<0.03; mean difference 0.99; 95% CI: -0.1-2.08), reported more vigor (NAP 4.44, NONE 2.39; p<0.03; mean difference 2.05; 95% CI: 0.63-3.47), less fatigue (NAP 7.4, NONE 10.43; p<0.05; mean difference 3.03; 95% CI: 1.11-4.95), and less sleepiness (NAP 5.36, NONE 6.48; p<0.03; mean difference 1.12; 95% CI: 0.41-1.83). They tended to more quickly complete the intravenous insertion (NAP 66.40 sec, NONE 86.48 sec; p=0.10; mean difference 20.08; 95% CI: 4.64-35.52), exhibit less dangerous driving and display fewer behavioral signs of sleepiness during the driving simulation. Immediately after the nap (4 AM), the subjects scored more poorly on Probed Recall Memory (NAP 2.76, NONE 3.7; p<0.05; mean difference 0.94; 95% CI: 0.20-1.68). A nap at 3 AM improved performance and subjective report in physicians and nurses at 7:30 AM compared to a no-nap condition. Immediately after the nap, memory temporarily

Sleep duration, nap habits, and mortality in older persons.

PubMed

Cohen-Mansfield, Jiska; Perach, Rotem

2012-07-01

To examine the effect of nighttime sleep duration on mortality and the effect modification of daytime napping on the relationship between nighttime sleep duration and mortality in older persons. Prospective survey with 20-yr mortality follow-up. The Cross-Sectional and Longitudinal Aging Study, a multidimensional assessment of a stratified random sample of the older Jewish population in Israel conducted between 1989-1992. There were 1,166 self-respondent, community-dwelling participants age 75-94 yr (mean, 83.40, standard deviation, 5.30). Nighttime sleep duration, napping, functioning (activities of daily living, instrumental activities of daily living, Orientation Memory Concentration Test), health, and mortality. Duration of nighttime sleep of more than 9 hr was significantly related to increased mortality in comparison with sleeping 7-9 hr (hazard ratio [HR] = 1.31, P < 0.01) after adjusting for demographic, health, and function variables, whereas for short nighttime sleep of fewer than 7 hr mortality did not differ from that of 7-9 hr of sleep. For those who nap, sleeping more than 9 hr per night significantly increased mortality risk (HR = 1.385, P < 0.05) and shorter nighttime sleep reduced mortality significantly in the unadjusted model (HR = 0.71, P < 0.001) but only approached significance in the fully adjusted model (HR = 0.82, P = 0.054). For those who do not or sometimes nap, a short amount of sleep appears to be harmful up to age 84 yr and may be protective thereafter (HR = 1.51, confidence interval [CI] = 1.13-2.02, P < 0.01; HR = 0.76, CI = 0.49-1.17, in the fully adjusted model, respectively). The findings are novel in demonstrating the protective effect of short nighttime sleep duration in individuals who take daily naps and suggest that the examination of the effect of sleep needs to take into account sleep duration per 24 hr, rather than daytime napping or nighttime sleep per se. Cohen-Mansfield J; Perach R. Sleep duration, nap habits, and

CSR-1 RNAi pathway positively regulates histone expression in C. elegans

PubMed Central

Avgousti, Daphne C; Palani, Santhosh; Sherman, Yekaterina; Grishok, Alla

2012-01-01

Endogenous small interfering RNAs (endo-siRNAs) have been discovered in many organisms, including mammals. In C. elegans, depletion of germline-enriched endo-siRNAs found in complex with the CSR-1 Argonaute protein causes sterility and defects in chromosome segregation in early embryos. We discovered that knockdown of either csr-1, the RNA-dependent RNA polymerase (RdRP) ego-1, or the dicer-related helicase drh-3, leads to defects in histone mRNA processing, resulting in severe depletion of core histone proteins. The maturation of replication-dependent histone mRNAs, unlike that of other mRNAs, requires processing of their 3′UTRs through an endonucleolytic cleavage guided by the U7 snRNA, which is lacking in C. elegans. We found that CSR-1-bound antisense endo-siRNAs match histone mRNAs and mRNA precursors. Consistently, we demonstrate that CSR-1 directly binds to histone mRNA in an ego-1-dependent manner using biotinylated 2′-O-methyl RNA oligonucleotides. Moreover, we demonstrate that increasing the dosage of histone genes rescues the lethality associated with depletion of CSR-1 and EGO-1. These results support a positive and direct effect of RNAi on histone gene expression. PMID:22863779

CSR-1 RNAi pathway positively regulates histone expression in C. elegans.

PubMed

Avgousti, Daphne C; Palani, Santhosh; Sherman, Yekaterina; Grishok, Alla

2012-10-03

Endogenous small interfering RNAs (endo-siRNAs) have been discovered in many organisms, including mammals. In C. elegans, depletion of germline-enriched endo-siRNAs found in complex with the CSR-1 Argonaute protein causes sterility and defects in chromosome segregation in early embryos. We discovered that knockdown of either csr-1, the RNA-dependent RNA polymerase (RdRP) ego-1, or the dicer-related helicase drh-3, leads to defects in histone mRNA processing, resulting in severe depletion of core histone proteins. The maturation of replication-dependent histone mRNAs, unlike that of other mRNAs, requires processing of their 3'UTRs through an endonucleolytic cleavage guided by the U7 snRNA, which is lacking in C. elegans. We found that CSR-1-bound antisense endo-siRNAs match histone mRNAs and mRNA precursors. Consistently, we demonstrate that CSR-1 directly binds to histone mRNA in an ego-1-dependent manner using biotinylated 2'-O-methyl RNA oligonucleotides. Moreover, we demonstrate that increasing the dosage of histone genes rescues the lethality associated with depletion of CSR-1 and EGO-1. These results support a positive and direct effect of RNAi on histone gene expression.

The chromatin-binding protein HMGN3 stimulates histone acetylation and transcription across the Glyt1 gene

PubMed Central

Barkess, Gráinne; Postnikov, Yuri; Campos, Chrisanne D.; Mishra, Shivam; Mohan, Gokula; Verma, Sakshi; Bustin, Michael; West, Katherine L.

2013-01-01

HMGNs are nucleosome-binding proteins that alter the pattern of histone modifications and modulate the binding of linker histones to chromatin. The HMGN3 family member exists as two splice forms, HMGN3a which is full-length and HMGN3b which lacks the C-terminal RD (regulatory domain). In the present study, we have used the Glyt1 (glycine transporter 1) gene as a model system to investigate where HMGN proteins are bound across the locus in vivo, and to study how the two HMGN3 splice variants affect histone modifications and gene expression. We demonstrate that HMGN1, HMGN2, HMGN3a and HMGN3b are bound across the Glyt1 gene locus and surrounding regions, and are not enriched more highly at the promoter or putative enhancer. We conclude that the peaks of H3K4me3 (trimethylated Lys4 of histone H3) and H3K9ac (acetylated Lys9 of histone H3) at the active Glyt1a promoter do not play a major role in recruiting HMGN proteins. HMGN3a/b binding leads to increased H3K14 (Lys14 of histone H3) acetylation and stimulates Glyt1a expression, but does not alter the levels of H3K4me3 or H3K9ac enrichment. Acetylation assays show that HMGN3a stimulates the ability of PCAF [p300/CREB (cAMP-response-element-binding protein)-binding protein-associated factor] to acetylate nucleosomal H3 in vitro, whereas HMGN3b does not. We propose a model where HMGN3a/b-stimulated H3K14 acetylation across the bodies of large genes such as Glyt1 can lead to more efficient transcription elongation and increased mRNA production. PMID:22150271

To nap or not to nap: excessive daytime napping is associated with elevated evening cortisol in nursing home residents with dementia.

PubMed

Woods, Diana Lynn; Kim, Haesook; Yefimova, Maria

2013-04-01

Alterations in the sleep-wake cycle, including daytime napping, are consistently reported in persons with dementia (PWD). A dysregulation in the hypothalamic-pituitary-adrenal (HPA) axis, indexed by elevated evening cortisol, may offer one explanation for these alterations. Alternatively, excessive daytime sleeping may alter cortisol rhythm and increase intraindividual variability, potentially contributing to increased environmental reactivity and behavioral symptoms. The purpose of this substudy (N = 12) was to examine the association between daytime napping and basal cortisol diurnal rhythm in nursing home residents with dementia. In this within-individual longitudinal design, saliva samples were obtained daily for 5 consecutive days upon waking and 30-45 min, 6 hr, and 12 hr after waking to obtain a cortisol diurnal rhythm. Behavior and sleep-wake state (nap/no nap) were observed and recorded every 20 min for 12 hr per day for 5 days. Participants were categorized as high nappers (HNs) or low nappers (LNs). There was a significant difference in evening cortisol levels (t = -2.38, p = .032) and continence (t = 3.37, p = .007) between groups, with HNs exhibiting higher evening cortisol levels. There were no other significant differences in resident characteristics between the two groups. These data suggest a link between excessive daytime napping and elevated evening cortisol in PWD consistent with findings in children. Elevated evening cortisol is an indication of a dysregulation in the HPA axis. These preliminary data support a close association between the sleep-wake cycle and HPA-axis regulation in PWD.

Antibodies to H1 histone from the sera of HIV-infected patients recognize and catalyze site-specific degradation of this histone.

PubMed

Baranova, Svetlana V; Dmitrienok, Pavel S; Ivanisenko, Nikita V; Buneva, Valentina N; Nevinsky, Georgy A

2017-03-01

Histones and their posttranslational modifications have key roles in chromatin remodeling and gene transcription. Besides intranuclear functions, histones act as damage-associated molecules when they are released into the extracellular space. Administration of histones to animals leads to systemic inflammatory and toxic responses. Autoantibodies with enzymatic activities (abzymes) are distinctive feature of some autoimmune and viral diseases. Electrophoretically and immunologically homogeneous IgGs containing no canonical enzymes were isolated from sera of human immunodeficiency virus-infected patients by chromatography on several affinity sorbents. In contrast to canonical proteases (trypsin, chymotrypsin, and proteinase K), IgGs from human immunodeficiency virus-infected patients purified by affinity chromatography on Sepharose containing immobilized histones specifically recognized and hydrolyzed only histones but not many other tested globular proteins. Using matrix-assisted laser desorption/ionization mass spectrometry, the sites of H1 histone (193 amino acids [AAs]) cleavage by anti-H1 histone IgGs were determined for the first time. It was shown that 1 cluster of 2 major and 4 moderate sites of cleavage is located at the beginning (106-112 AAs) of the known antigenic determinants disposed at the long C-terminal sequence of H1. Two clusters of minor and very weak sites of the protein cleavage correspond to middle (8 sites, 138-158 AAs) and terminal (5 sites, 166-176 AAs) parts of the antigenic determinants. It was shown that in contrast to canonical proteases, N-terminal part of H1 histone (1-136 AAs) containing no antigenic determinants is an unpredictably very resistant against hydrolysis by abzymes, while it can be easily cleavage by canonical proteases. Because histones act as damage-associated molecules, abzymes against H1 and other histones can play important role in pathogenesis of acquired immune deficiency syndrome and probably other different

Characteristics of napping in community-dwelling insomnia patients.

PubMed

Jang, Kwang Ho; Lee, Jung Hie; Kim, Seong Jae; Kwon, Hyo Jeong

2018-05-01

We aimed to determine napping characteristics of community-dwelling patients with insomnia disorder (ID) compared to characteristics of normal controls (NC), and to examine the effect of napping on nocturnal sleep. Adult volunteers who were more than 18 years old were recruited from three rural public health centers in Korea. Data from actigraphy recording and a sleep diary filled out for seven days were obtained. Finally, 115 ID patients and 80 NC subjects were included in this study. Parameters and timing of nocturnal sleep and nap were compared between the ID and NC groups. Two-way analysis of covariance (ANCOVA) was performed to determine the effect of ID diagnosis and napping on sleep parameters. Sleep efficiency (SE) in the ID group was significantly lower (p = 0.010), and wake time after sleep onset (WASO) was significantly greater (p = 0.023), compared to the NC group. There was no significant difference in nocturnal sleep or nap timing between the two groups. Nap frequency in the ID group was significantly higher than that in the NC group (p = 0.025). Although ID diagnosis and napping had no independent effect on fragmentation index, their interaction had a significant effect on fragmentation index (p = 0.021). Nap frequency was positively correlated with PSQI score (r = 0.166, p = 0.033). Insomnia patients showed no significant difference in nap timing or nap duration compared to NC subjects. However, insomnia patients showed higher nap frequency. Frequent napping was associated with poorer subjective sleep quality. Therefore, although napping might not have a negative impact on nocturnal sleep maintenance in NC subjects, it did have an effect on nocturnal sleep in insomnia patients. Copyright © 2018 Elsevier B.V. All rights reserved.

Napping and Nighttime Sleep: Findings From an Occupation-Based Intervention

PubMed Central

Fogelberg, Donald; Sleight, Alix; Mallinson, Trudy; Vigen, Cheryl; Blanchard, Jeanine; Carlson, Mike; Clark, Florence

2016-01-01

OBJECTIVE. To describe sleeping behaviors and trends over time among an ethnically diverse group of community-living older adults. METHOD. A descriptive secondary data analysis of a subsample (n = 217) from the Lifestyle Redesign randomized controlled trial was done to explore baseline napping and sleeping patterns as well as 6-mo changes in these outcomes. RESULTS. At baseline, the average time sleeping was 8.2 hr daily (standard deviation = 1.7). Among all participants, 29% reported daytime napping at baseline, of which 36% no longer napped at follow-up. Among participants who stopped napping, those who received an occupation-based intervention (n = 98) replaced napping time with nighttime sleep, and those not receiving an intervention (n = 119) experienced a net loss of total sleep (p < .05). CONCLUSION. Among participants who stopped napping, the occupation-based intervention may be related to enhanced sleep. More research examining the role of occupation-based interventions in improving sleep is warranted. PMID:27294991

Napping and Nighttime Sleep: Findings From an Occupation-Based Intervention.

PubMed

Leland, Natalie E; Fogelberg, Donald; Sleight, Alix; Mallinson, Trudy; Vigen, Cheryl; Blanchard, Jeanine; Carlson, Mike; Clark, Florence

2016-01-01

To describe sleeping behaviors and trends over time among an ethnically diverse group of community-living older adults. A descriptive secondary data analysis of a subsample (n = 217) from the Lifestyle Redesign randomized controlled trial was done to explore baseline napping and sleeping patterns as well as 6-mo changes in these outcomes. At baseline, the average time sleeping was 8.2 hr daily (standard deviation = 1.7). Among all participants, 29% reported daytime napping at baseline, of which 36% no longer napped at follow-up. Among participants who stopped napping, those who received an occupation-based intervention (n = 98) replaced napping time with nighttime sleep, and those not receiving an intervention (n = 119) experienced a net loss of total sleep (p < .05). Among participants who stopped napping, the occupation-based intervention may be related to enhanced sleep. More research examining the role of occupation-based interventions in improving sleep is warranted. Copyright © 2016 by the American Occupational Therapy Association, Inc.

Daytime napping and increased risk of incident respiratory diseases: symptom, marker, or risk factor?

PubMed

Leng, Yue; Wainwright, Nick W J; Cappuccio, Francesco P; Surtees, Paul G; Hayat, Shabina; Luben, Robert; Brayne, Carol; Khaw, Kay-Tee

2016-07-01

We have identified a strong association between daytime napping and increased mortality risk from respiratory diseases, but little is known about the relationship between daytime napping and respiratory morbidity. Data were drawn from the European Prospective Investigation into Cancer and Nutrition-Norfolk cohort. Participants reported napping habits during 1998-2000 and were followed up for respiratory disease hospital admissions until March 2009. Cox proportional hazards regression was used to examine the association between daytime napping and respiratory disease incidence risk. The study sample included 10,978 men and women with a mean age of 61.9 years, and a total of 946 incident respiratory disease cases were recorded. After adjustment for age, sex, social class, education, marital status, employment status, nightshift work, body mass index, physical activity, smoking, alcohol intake, self-reported general health, hypnotic drug use, habitual sleep duration, and preexisting health conditions, daytime napping was associated with an increase in the overall respiratory disease incidence risk (hazard ratio (HR) = 1.32, 95% confidence interval (CI) 1.15, 1.52 for napping <1 h; HR = 1.54, 95% CI 1.14, 2.09 for napping ≥1 h). This association was more pronounced for lower respiratory diseases, especially for the risk of chronic lower respiratory diseases (HR = 1.52, 95% CI: 1.18, 1.96 for napping <1 h; HR = 1.72, 95% CI: 1.01, 2.92 for napping ≥1 h, overall p = 0.003). Excessive daytime napping might be a useful marker of future respiratory disease incidence risk. Further studies are required to confirm these findings and help understand potential mechanisms. Copyright © 2016 The Author(s). Published by Elsevier B.V. All rights reserved.

Replication-dependent histone genes are actively transcribed in differentiating and aging retinal neurons

PubMed Central

Banday, Abdul Rouf; Baumgartner, Marybeth; Al Seesi, Sahar; Karunakaran, Devi Krishna Priya; Venkatesh, Aditya; Congdon, Sean; Lemoine, Christopher; Kilcollins, Ashley M; Mandoiu, Ion; Punzo, Claudio; Kanadia, Rahul N

2014-01-01

In the mammalian genome, each histone family contains multiple replication-dependent paralogs, which are found in clusters where their transcription is thought to be coupled to the cell cycle. Here, we wanted to interrogate the transcriptional regulation of these paralogs during retinal development and aging. We employed deep sequencing, quantitative PCR, in situ hybridization (ISH), and microarray analysis, which revealed that replication-dependent histone genes were not only transcribed in progenitor cells but also in differentiating neurons. Specifically, by ISH analysis we found that different histone genes were actively transcribed in a subset of neurons between postnatal day 7 and 14. Interestingly, within a histone family, not all paralogs were transcribed at the same level during retinal development. For example, expression of Hist1h1b was higher embryonically, while that of Hist1h1c was higher postnatally. Finally, expression of replication-dependent histone genes was also observed in the aging retina. Moreover, transcription of replication-dependent histones was independent of rapamycin-mediated mTOR pathway inactivation. Overall, our data suggest the existence of variant nucleosomes produced by the differential expression of the replication-dependent histone genes across retinal development. Also, the expression of a subset of replication-dependent histone isotypes in senescent neurons warrants re-examining these genes as “replication-dependent.” Thus, our findings underscore the importance of understanding the transcriptional regulation of replication-dependent histone genes in the maintenance and functioning of neurons. PMID:25486194

The Histone Demethylase Jhdm1a Regulates Hepatic Gluconeogenesis

PubMed Central

Zou, Tie; Yao, Annie Y.; Cooper, Marcus P.; Boyartchuk, Victor; Wang, Yong-Xu

2012-01-01

Hepatic gluconeogenesis is required for maintaining blood glucose homeostasis; yet, in diabetes mellitus, this process is unrestrained and is a major contributor to fasting hyperglycemia. To date, the impacts of chromatin modifying enzymes and chromatin landscape on gluconeogenesis are poorly understood. Through catalyzing the removal of methyl groups from specific lysine residues in the histone tail, histone demethylases modulate chromatin structure and, hence, gene expression. Here we perform an RNA interference screen against the known histone demethylases and identify a histone H3 lysine 36 (H3K36) demethylase, Jhdm1a, as a key negative regulator of gluconeogenic gene expression. In vivo, silencing of Jhdm1a promotes liver glucose synthesis, while its exogenous expression reduces blood glucose level. Importantly, the regulation of gluconeogenesis by Jhdm1a requires its demethylation activity. Mechanistically, we find that Jhdm1a regulates the expression of a major gluconeogenic regulator, C/EBPα. This is achieved, at least in part, by its USF1-dependent association with the C/EBPα promoter and its subsequent demethylation of dimethylated H3K36 on the C/EBPα locus. Our work provides compelling evidence that links histone demethylation to transcriptional regulation of gluconeogenesis and has important implications for the treatment of diabetes. PMID:22719268

Association of class II histone deacetylases with heterochromatin protein 1: potential role for histone methylation in control of muscle differentiation.

PubMed

Zhang, Chun Li; McKinsey, Timothy A; Olson, Eric N

2002-10-01

Class II histone deacetylases (HDACs) 4, 5, 7, and 9 repress muscle differentiation through associations with the myocyte enhancer factor 2 (MEF2) transcription factor. MEF2-interacting transcription repressor (MITR) is an amino-terminal splice variant of HDAC9 that also potently inhibits MEF2 transcriptional activity despite lacking a catalytic domain. Here we report that MITR, HDAC4, and HDAC5 associate with heterochromatin protein 1 (HP1), an adaptor protein that recognizes methylated lysines within histone tails and mediates transcriptional repression by recruiting histone methyltransferase. Promyogenic signals provided by calcium/calmodulin-dependent kinase (CaMK) disrupt the interaction of MITR and HDACs with HP1. Since the histone methyl-lysine residues recognized by HP1 also serve as substrates for deacetylation by HDACs, the interaction of MITR and HDACs with HP1 provides an efficient mechanism for silencing MEF2 target genes by coupling histone deacetylation and methylation. Indeed, nucleosomal histones surrounding a MEF2-binding site in the myogenin gene promoter are highly methylated in undifferentiated myoblasts, when the gene is silent, and become acetylated during muscle differentiation, when the myogenin gene is expressed at high levels. The ability of MEF2 to recruit a histone methyltransferase to target gene promoters via HP1-MITR and HP1-HDAC interactions and of CaMK signaling to disrupt these interactions provides an efficient mechanism for signal-dependent regulation of the epigenetic events controlling muscle differentiation.

Association of Class II Histone Deacetylases with Heterochromatin Protein 1: Potential Role for Histone Methylation in Control of Muscle Differentiation

PubMed Central

Zhang, Chun Li; McKinsey, Timothy A.; Olson, Eric N.

2002-01-01

Class II histone deacetylases (HDACs) 4, 5, 7, and 9 repress muscle differentiation through associations with the myocyte enhancer factor 2 (MEF2) transcription factor. MEF2-interacting transcription repressor (MITR) is an amino-terminal splice variant of HDAC9 that also potently inhibits MEF2 transcriptional activity despite lacking a catalytic domain. Here we report that MITR, HDAC4, and HDAC5 associate with heterochromatin protein 1 (HP1), an adaptor protein that recognizes methylated lysines within histone tails and mediates transcriptional repression by recruiting histone methyltransferase. Promyogenic signals provided by calcium/calmodulin-dependent kinase (CaMK) disrupt the interaction of MITR and HDACs with HP1. Since the histone methyl-lysine residues recognized by HP1 also serve as substrates for deacetylation by HDACs, the interaction of MITR and HDACs with HP1 provides an efficient mechanism for silencing MEF2 target genes by coupling histone deacetylation and methylation. Indeed, nucleosomal histones surrounding a MEF2-binding site in the myogenin gene promoter are highly methylated in undifferentiated myoblasts, when the gene is silent, and become acetylated during muscle differentiation, when the myogenin gene is expressed at high levels. The ability of MEF2 to recruit a histone methyltransferase to target gene promoters via HP1-MITR and HP1-HDAC interactions and of CaMK signaling to disrupt these interactions provides an efficient mechanism for signal-dependent regulation of the epigenetic events controlling muscle differentiation. PMID:12242305

The WD40 Domain Protein MSI1 Functions in a Histone Deacetylase Complex to Fine-Tune Abscisic Acid Signaling.

PubMed

Mehdi, Saher; Derkacheva, Maria; Ramström, Margareta; Kralemann, Lejon; Bergquist, Jonas; Hennig, Lars

2016-01-01

MSI1 belongs to a family of histone binding WD40-repeat proteins. Arabidopsis thaliana contains five genes encoding MSI1-like proteins, but their functions in diverse chromatin-associated complexes are poorly understood. Here, we show that MSI1 is part of a histone deacetylase complex. We copurified HISTONE DEACETYLASE19 (HDA19) with MSI1 and transcriptional regulatory SIN3-like proteins and provide evidence that MSI1 and HDA19 associate into the same complex in vivo. These data suggest that MSI1, HDA19, and HISTONE DEACETYLATION COMPLEX1 protein form a core complex that can integrate various SIN3-like proteins. We found that reduction of MSI1 or HDA19 causes upregulation of abscisic acid (ABA) receptor genes and hypersensitivity of ABA-responsive genes. The MSI1-HDA19 complex fine-tunes ABA signaling by binding to the chromatin of ABA receptor genes and by maintaining low levels of acetylation of histone H3 at lysine 9, thereby affecting the expression levels of ABA receptor genes. Reduced MSI1 or HDA19 levels led to increased tolerance to salt stress corresponding to the increased ABA sensitivity of gene expression. Together, our results reveal the presence of an MSI1-HDA19 complex that fine-tunes ABA signaling in Arabidopsis. © 2016 American Society of Plant Biologists. All rights reserved.

Involvement of Retinoblastoma Protein and HBP1 in Histone H10 Gene Expression

PubMed Central

Lemercier, Claudie; Duncliffe, Kym; Boibessot, Isabelle; Zhang, Hui; Verdel, André; Angelov, Dimitar; Khochbin, Saadi

2000-01-01

The histone H10-encoding gene is expressed in vertebrates in differentiating cells during the arrest of proliferation. In the H10 promoter, a specific regulatory element, which we named the H4 box, exhibits features which implicate a role in mediating H10 gene expression in response to both differentiation and cell cycle control signals. For instance, within the linker histone gene family, the H4 box is found only in the promoters of differentiation-associated subtypes, suggesting that it is specifically involved in differentiation-dependent expression of these genes. In addition, an element nearly identical to the H4 box is conserved in the promoters of histone H4-encoding genes and is known to be involved in their cell cycle-dependent expression. The transcription factors interacting with the H10 H4 box were therefore expected to link differentiation-dependent expression of H10 to the cell cycle control machinery. The aim of this work was to identify such transcription factors and to obtain information concerning the regulatory pathway involved. Interestingly, our cloning strategy led to the isolation of a retinoblastoma protein (RB) partner known as HBP1. HBP1, a high-mobility group box transcription factor, interacted specifically with the H10 H4 box and moreover was expressed in a differentiation-dependent manner. We also showed that the HBP1-encoding gene is able to produce different forms of HBP1. Finally, we demonstrated that both HBP1 and RB were involved in the activation of H10 gene expression. We therefore propose that HBP1 mediates a link between the cell cycle control machinery and cell differentiation signals. Through modulating the expression of specific chromatin-associated proteins such as histone H10, HBP1 plays a vital role in chromatin remodeling events during the arrest of cell proliferation in differentiating cells. PMID:10958660

Predominance and high antibiotic resistance of the emerging Clostridium difficile genotypes NAPCR1 and NAP9 in a Costa Rican hospital over a 2-year period without outbreaks.

PubMed

López-Ureña, Diana; Quesada-Gómez, Carlos; Montoya-Ramírez, Mónica; del Mar Gamboa-Coronado, María; Somogyi, Teresita; Rodríguez, César; Rodríguez-Cavallini, Evelyn

2016-05-11

Clostridium difficile is the major causative agent of nosocomial antibiotic-associated diarrhea. In a 2009 outbreak of C. difficile-associated diarrhea that was recorded in a major Costa Rican hospital, the hypervirulent NAP1 strain (45%) predominated together with a local genotype variant (NAPCR1, 31%). Both strains were fluoroquinolone-resistant and the NAPCR1 genotype, in addition, was resistant to clindamycin and rifampicin. We now report on the genotypes and antibiotic susceptibilities of 68 C. difficile isolates from a major Costa Rican hospital over a 2-year period without outbreaks. In contrast to our previous findings, no NAP1 strains were detected, and for the first time in a Costa Rican hospital, a significant fraction of the isolates were NAP9 strains (n=14, 21%). The local NAPCR1 genotype remained prevalent (n=18, 26%) and coexisted with 14 strains (21%) of classic hospital NAP types (NAP2, NAP4, and NAP6), eight new genotypes (12%), four environmental strains classified as NAP10 or NAP11 (6%), three strains without NAP designation (4%) and seven non-toxigenic strains (10%). All 68 strains were resistant to ciprofloxacin, 88% were resistant to clindamycin and 50% were resistant to moxifloxacin and rifampicin. Metronidazole and vancomycin susceptibilities were universal. The NAPCR1 and NAP9 strains, which have been associated with more severe clinical infections, were more resistant to antibiotics than the other strains. Altogether, our results confirm that the epidemiology of C. difficile infection is dynamic and that A(-)B(+) strains from the NAP9 type are on the rise not only in the developed world. Moreover, our results reveal that the local NAPCR1 strains still circulate in the country without causing outbreaks but with equally high antibiotic-resistance rates and levels.

The effects of napping on cognitive function in preschoolers.

PubMed

Lam, Janet C; Mahone, E Mark; Mason, Thornton; Scharf, Steven M

2011-01-01

To determine the relationship between napping and cognitive function in preschool-aged children. Daytime napping, nighttime sleep, and cognitive function were assessed in 59 typically developing children aged 3 to 5 years, who were enrolled in full-time childcare. Participants wore an actigraphy watch for 7 days to measure sleep and napping patterns and completed neuropsychological testing emphasizing attention, response control, and vocabulary. Parents of participants completed behavior ratings and sleep logs during the study. Sleep/wake cycles were scored with the Sadeh algorithm. Children who napped more on weekdays were also more likely to nap during weekends. Weekday napping and nighttime sleep were inversely correlated, such that those who napped more slept less at night, although total weekday sleep remained relatively constant. Weekday napping was significantly (negatively) correlated with vocabulary and auditory attention span, and weekday nighttime sleep was positively correlated with vocabulary. Nighttime sleep was also significantly negatively correlated with performance, such that those who slept less at night made more impulsive errors on a computerized go/no-go test. Daytime napping is actually negatively correlated with neurocognitive function in preschoolers. Nighttime sleep seems to be more critical for development of cognitive performance. Cessation of napping may serve as a developmental milestone of brain maturation. Children who nap less do not appear to be sleep deprived, especially if they compensate with increased nighttime sleep. An alternative explanation is that children who sleep less at night are sleep deprived and require a nap. A randomized trial of nap restriction would be the next step in understanding the relationship between napping and neurocognitive performance.

The Effects of Napping on Cognitive Function in Preschoolers

PubMed Central

Lam, Janet C.; Mahone, E. Mark; Mason, Thornton B.A.; Scharf, Steven M.

2011-01-01

Objective To determine the relationship between napping and cognitive function in preschool-aged children. Methods Daytime napping, nighttime sleep and cognitive function were assessed in fifty-nine typically developing children ages 3-5 years, who were enrolled in full-time childcare. Participants wore an actigraphy watch for 7 days to measure sleep and napping patterns, and completed neuropsychological testing emphasizing attention, response control, and vocabulary. Parents of participants completed behavior ratings and sleep logs during the study. Sleep/wake cycles were scored with the Sadeh algorithm. Results Children who napped more on weekdays were also more likely to nap during weekends. Weekday napping and nighttime sleep were inversely correlated, such that those who napped more slept less at night, while total weekday sleep remained relatively constant. Weekday napping was significantly (negatively) correlated with vocabulary and auditory attention span, and weekday nighttime sleep was positively correlated with vocabulary. Nighttime sleep was also significantly negatively correlated with performance, such that those who slept less at night made more impulsive errors on a computerized go/no-go test. Conclusions Daytime napping is actually negatively correlated with neurocognitive function in preschoolers. Nighttime sleep appears to be more critical for development of cognitive performance. Cessation of napping may serve as a developmental milestone of brain maturation. Children who nap less do not appear to be sleep deprived, especially if they compensate with increased nighttime sleep. An alternative explanation is that children who sleep less at night are sleep deprived and require a nap. A randomized trial of nap restriction would be the next step in understanding the relationship between napping and neurocognitive performance. PMID:21217402

Daydreams and nap dreams: Content comparisons.

PubMed

Carr, Michelle; Nielsen, Tore

2015-11-01

Differences between nighttime REM and NREM dreams are well-established but only rarely are daytime REM and NREM nap dreams compared with each other or with daydreams. Fifty-one participants took daytime naps (with REM or NREM awakenings) and provided both waking daydream and nap dream reports. They also provided ratings of their bizarreness, sensory experience, and emotion intensity. Recall rates for REM (96%) and NREM (89%) naps were elevated compared to typical recall rates for nighttime dreams (80% and 43% respectively), suggesting an enhanced circadian influence. All attribute ratings were higher for REM than for NREM dreams, replicating findings for nighttime dreams. Compared with daydreams, NREM dreams had lower ratings for emotional intensity and sensory experience while REM dreams had higher ratings for bizarreness and sensory experience. Results support using daytime naps in dream research and suggest that there occurs selective enhancement and inhibition of specific dream attributes by REM, NREM and waking state mechanisms. Copyright © 2015 Elsevier Inc. All rights reserved.

Meta-Analysis of Self-Reported Daytime Napping and Risk of Cardiovascular or All-Cause Mortality

PubMed Central

Liu, Xiaokun; Zhang, Qi; Shang, Xiaoming

2015-01-01

Background Whether self-reported daytime napping is an independent predictor of cardiovascular or all-cause mortality remains unclear. The aim of this study was to investigate self-reported daytime napping and risk of cardiovascular or all-cause mortality by conducting a meta-analysis. Material/Methods A computerized literature search of PubMed, Embase, and Cochrane Library was conducted up to May 2014. Only prospective studies reporting risk ratio (RR) and corresponding 95% confidence intervals (CI) of cardiovascular or all-cause mortality with respect to baseline self-reported daytime napping were included. Results Seven studies with 98,163 subjects were included. Self-reported daytime napping was associated with a greater risk of all-cause mortality (RR 1.15; 95% CI 1.07–1.24) compared with non-nappers. Risk of all-cause mortality appeared to be more pronounced among persons with nap duration >60 min (RR 1.15; 95% CI 1.04–1.27) than persons with nap duration <60 min (RR 1.10; 95% CI 0.92–1.32). The pooled RR of cardiovascular mortality was 1.19 (95% CI 0.97–1.48) comparing daytime nappers to non-nappers. Conclusions Self-reported daytime napping is a mild but statistically significant predictor for all-cause mortality, but not for cardiovascular mortality. However, whether the risk is attributable to excessive sleep duration or napping alone remains controversial. More prospective studies stratified by sleep duration, napping periods, or age are needed. PMID:25937468

Meta-analysis of self-reported daytime napping and risk of cardiovascular or all-cause mortality.

PubMed

Liu, Xiaokun; Zhang, Qi; Shang, Xiaoming

2015-05-04

Whether self-reported daytime napping is an independent predictor of cardiovascular or all-cause mortality remains unclear. The aim of this study was to investigate self-reported daytime napping and risk of cardiovascular or all-cause mortality by conducting a meta-analysis. A computerized literature search of PubMed, Embase, and Cochrane Library was conducted up to May 2014. Only prospective studies reporting risk ratio (RR) and corresponding 95% confidence intervals (CI) of cardiovascular or all-cause mortality with respect to baseline self-reported daytime napping were included. Seven studies with 98,163 subjects were included. Self-reported daytime napping was associated with a greater risk of all-cause mortality (RR 1.15; 95% CI 1.07-1.24) compared with non-nappers. Risk of all-cause mortality appeared to be more pronounced among persons with nap duration >60 min (RR 1.15; 95% CI 1.04-1.27) than persons with nap duration <60 min (RR 1.10; 95% CI 0.92-1.32). The pooled RR of cardiovascular mortality was 1.19 (95% CI 0.97-1.48) comparing daytime nappers to non-nappers. Self-reported daytime napping is a mild but statistically significant predictor for all-cause mortality, but not for cardiovascular mortality. However, whether the risk is attributable to excessive sleep duration or napping alone remains controversial. More prospective studies stratified by sleep duration, napping periods, or age are needed.

Daytime napping associated with increased symptom severity in fibromyalgia syndrome.

PubMed

Theadom, Alice; Cropley, Mark; Kantermann, Thomas

2015-02-07

Previous qualitative research has revealed that people with fibromyalgia use daytime napping as a coping strategy for managing symptoms against clinical advice. Yet there is no evidence to suggest whether daytime napping is beneficial or detrimental for people with fibromyalgia. The purpose of this study was to explore how people use daytime naps and to determine the links between daytime napping and symptom severity in fibromyalgia syndrome. A community based sample of 1044 adults who had been diagnosed with fibromyalgia syndrome by a clinician completed an online questionnaire. Associations between napping behavior, sleep quality and fibromyalgia symptoms were explored using Spearman correlations, with possible predictors of napping behaviour entered into a logistic regression model. Differences between participants who napped on a daily basis and those who napped less regularly, as well as nap duration were explored. Daytime napping was significantly associated with increased pain, depression, anxiety, fatigue, memory difficulties and sleep problems. Sleep problems and fatigue explained the greatest amount of variance in napping behaviour, p < 0.010. Those who engaged in daytime naps for >30 minutes had higher memory difficulties (t = -3.45) and levels of depression (t = -2.50) than those who napped for shorter periods (<30 mins) (p < 0.010). Frequent use and longer duration of daytime napping was linked with greater symptom severity in people with fibromyalgia. Given the common use of daytime napping in people with fibromyalgia evidence based guidelines on the use of daytime napping in people with chronic pain are urgently needed.

Napping and associated factors: a Japanese nationwide general population survey.

PubMed

Furihata, Ryuji; Kaneita, Yoshitaka; Jike, Maki; Ohida, Takashi; Uchiyama, Makoto

2016-04-01

The objective of this study was to investigate napping habits and their associated factors in the Japanese adult general population. The cross-sectional survey was conducted in November 2007 for subjects selected randomly from among 300 districts throughout Japan. Data from 7664 people (3527 men and 4137 women), aged 20-99 years, were analyzed. Participants completed a self-administered questionnaire on frequency and duration of napping. The percentage of responders for high-frequency napping, four or more days per week, was 21.2% among men and 17.1% among women. The percentage of responders for long-duration napping, 2 h or more per one nap, was 2.9% among men and 2.6% among women. Multivariate logistic regression analyses revealed that men, older age, smoking, insomnia symptoms, long sleep duration, excessive daytime sleepiness, and having sufficient rest obtained by sleep were positively associated with high-frequency napping, whereas alcohol drinking showed a negative association. Older age was negatively associated with long-duration napping whereas living in a large community, smoking, long sleep duration, excessive daytime sleepiness, and psychological stress showed a positive association. These findings provide important data for future studies aimed at improvement of sleep habits. Copyright © 2016 Elsevier B.V. All rights reserved.

Napping facilitates word learning in early lexical development.

PubMed

Horváth, Klára; Myers, Kyle; Foster, Russell; Plunkett, Kim

2015-10-01

Little is known about the role that night-time sleep and daytime naps play in early cognitive development. Our aim was to investigate how napping affects word learning in 16-month-olds. Thirty-four typically developing infants were assigned randomly to nap and wake groups. After teaching two novel object-word pairs to infants, we tested their initial performance with an intermodal preferential looking task in which infants are expected to increase their target looking time compared to a distracter after hearing its auditory label. A second test session followed after approximately a 2-h delay. The delay contained sleep for the nap group or no sleep for the wake group. Looking behaviour was measured with an automatic eye-tracker. Vocabulary size was assessed using the Oxford Communicative Development Inventory. A significant interaction between group and session was found in preferential looking towards the target picture. The performance of the nap group increased after the nap, whereas that of the wake group did not change. The gain in performance correlated positively with the expressive vocabulary size in the nap group. These results indicate that daytime napping helps consolidate word learning in infancy. © 2015 European Sleep Research Society.

A novel non-SET domain multi-subunit methyltransferase required for sequential nucleosomal histone H3 methylation by the mixed lineage leukemia protein-1 (MLL1) core complex.

PubMed

Patel, Anamika; Vought, Valarie E; Dharmarajan, Venkatasubramanian; Cosgrove, Michael S

2011-02-04

Gene expression within the context of eukaryotic chromatin is regulated by enzymes that catalyze histone lysine methylation. Histone lysine methyltransferases that have been identified to date possess the evolutionarily conserved SET or Dot1-like domains. We previously reported the identification of a new multi-subunit histone H3 lysine 4 methyltransferase lacking homology to the SET or Dot1 family of histone lysine methyltransferases. This enzymatic activity requires a complex that includes WRAD (WDR5, RbBP5, Ash2L, and DPY-30), a complex that is part of the MLL1 (mixed lineage leukemia protein-1) core complex but that also exists independently of MLL1 in the cell. Here, we report that the minimal complex required for WRAD enzymatic activity includes WDR5, RbBP5, and Ash2L and that DPY-30, although not required for enzymatic activity, increases the histone substrate specificity of the WRAD complex. We also show that WRAD requires zinc for catalytic activity, displays Michaelis-Menten kinetics, and is inhibited by S-adenosyl-homocysteine. In addition, we demonstrate that WRAD preferentially methylates lysine 4 of histone H3 within the context of the H3/H4 tetramer but does not methylate nucleosomal histone H3 on its own. In contrast, we find that MLL1 and WRAD are required for nucleosomal histone H3 methylation, and we provide evidence suggesting that each plays distinct structural and catalytic roles in the recognition and methylation of a nucleosome substrate. Our results indicate that WRAD is a new H3K4 methyltransferase with functions that include regulating the substrate and product specificities of the MLL1 core complex.

CE: Original Research: Napping on the Night Shift: A Two-Hospital Implementation Project.

PubMed

Geiger-Brown, Jeanne; Sagherian, Knar; Zhu, Shijun; Wieroniey, Margaret Ann; Blair, Lori; Warren, Joan; Hinds, Pamela S; Szeles, Rose

2016-05-01

: Nurses who work the night shift often experience high levels of sleepiness. Napping has been adopted as an effective countermeasure to sleepiness and fatigue in other safety-sensitive industries, but has not had widespread acceptance in nursing. To assess the barriers to successful implementation of night-shift naps and to describe the nap experiences of night-shift nurses who took naps. In this two-hospital pilot implementation project, napping on the night shift was offered to six nursing units for which the executive nursing leadership had given approval. Unit nurse managers' approval was sought, and where granted, further explanation was given to the unit's staff nurses. A nap experience form, which included the Karolinska Sleepiness Scale, was used to assess pre-nap sleepiness level, nap duration and perceived sleep experience, post-nap sleep inertia, and the perceived helpfulness of the nap. Nurse managers and staff nurses were also interviewed at the end of the three-month study period. Successful implementation occurred on only one of the six units, with partial success seen on a second unit. Barriers primarily occurred at the point of seeking the unit nurse managers' approval. On the successful unit, 153 30-minutes naps were taken during the study period. A high level of sleepiness was present at the beginning of 44% of the naps. For more than half the naps, nurses reported achieving either light (43%) or deep (14%) sleep. Sleep inertia was rare. The average score of helpfulness of napping was high (7.3 on a 1-to-10 scale). Nurses who napped reported being less drowsy while driving home after their shift. These data suggest that when barriers to napping are overcome, napping on the night shift is feasible and can reduce nurses' workplace sleepiness and drowsy driving on the way home. Addressing nurse managers' perceptions of and concerns about napping may be essential to successful implementation.

EPC1/TIP60-Mediated Histone Acetylation Facilitates Spermiogenesis in Mice.

PubMed

Dong, Yixin; Isono, Kyo-Ichi; Ohbo, Kazuyuki; Endo, Takaho A; Ohara, Osamu; Maekawa, Mamiko; Toyama, Yoshiro; Ito, Chizuru; Toshimori, Kiyotaka; Helin, Kristian; Ogonuki, Narumi; Inoue, Kimiko; Ogura, Atsuo; Yamagata, Kazutsune; Kitabayashi, Issay; Koseki, Haruhiko

2017-10-01

Global histone hyperacetylation is suggested to play a critical role for replacement of histones by transition proteins and protamines to compact the genome during spermiogenesis. However, the underlying mechanisms for hyperacetylation-mediated histone replacement remains poorly understood. Here, we report that EPC1 and TIP60, two critical components of the mammalian nucleosome acetyltransferase of H4 (NuA4) complexes, are coexpressed in male germ cells. Strikingly, genetic ablation of either Epc1 or Tip60 disrupts hyperacetylation and impairs histone replacement, in turn causing aberrant spermatid development. Taking these observations together, we reveal an essential role of the NuA4 complexes for histone hyperacetylation and subsequent compaction of the spermatid genome. Copyright © 2017 American Society for Microbiology.

Day napping and short night sleeping are associated with higher risk of diabetes in older adults.

PubMed

Xu, Qun; Song, Yiqing; Hollenbeck, Albert; Blair, Aaron; Schatzkin, Arthur; Chen, Honglei

2010-01-01

To examine whether day napping or short night sleeping is associated with higher risk of diabetes. This was a prospective study of hours of day napping and night sleeping assessed in 1996-1997 in relation to diabetes diagnosed between 2000 and 2006 (n = 10,143) among 174,542 participants in the National Institutes of Health (NIH)-AARP Diet and Health Study. Odds ratios (ORs) and 95% CI were derived from multivariate logistic regression models. Longer day napping was associated with a higher risk of diabetes. After adjustment for potential confounders, ORs were 1.23 (95% CI 1.18-1.29) for those reporting <1 h and 1.55 (95% CI 1.45-1.66) for those reporting > or =1 h of napping compared with individuals who did not nap (P(trend) < 0.0001). For night sleeping, with 7-8 h as the referent, the OR was 1.46 (95% CI 1.31-1.63) for <5 h, 1.11 (1.06-1.16) for 5-6 h, and 1.11 (0.99-1.24) for > or =9 h. In both analyses, additional adjustment for BMI only modestly attenuated the associations. Further analysis showed a statistically significant interaction between hours of napping and sleeping on diabetes (P(interaction) < 0.0001). Among participants with no napping, only short night sleeping was associated with higher occurrence of diabetes, whereas among those with > or =1 h of napping, both long and short sleeping was associated with higher risk. Day napping and short night sleeping are associated with higher risk of diabetes. The association between sleep duration and diabetes may be modified by napping habit.

The Influence of Match-Day Napping in Elite Female Netball Athletes.

PubMed

O'Donnell, Shannon; Beaven, Christopher M; Driller, Matthew

2018-03-15

To assess the effect of match-day napping and duration of naps on perceptual and performance indices in elite female netball players over two consecutive netball seasons. Fourteen elite female netball athletes (mean ± SD; age = 23 ± 6 yr) participated in an observational study over 26 competition matches. On each match day, athletes provided information on their napping habits, perceived energy levels, and then performed 3 countermovement jumps (CMJ) 3h30 prior to the start of the match. One hour following the match, subjective player performance ratings from the players and two members of the coaching staff were obtained. Naps were characterized into 3 conditions for analysis; No Nap (NN), <20 min Nap (SHORT), and ≥20 min Nap (LONG). A significant difference in peak jump velocity was observed between the SHORT and the NN condition in favor of the shorter nap (3.23 ± 0.26 and 3.07 ± 0.36 m.s -1 , respectively, d = 0.34, p < 0.05). A moderate, significant difference (d = 0.85; p < 0.05) was observed for the coach rating of performance (out of 10) between the SHORT and the NN condition (7.2 ± 0.8 and 6.4 ± 0.9, respectively) in favor of SHORT. The findings from the study would suggest that a short nap (<20 min) on the day of competition can enhance jump velocity and improve subjective performance in elite netball players, as assessed by coaching staff.

Murine hematopoietic stem cell dormancy controlled by induction of a novel short form of PSF1 by histone deacetylase inhibitors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, Yinglu; Gong, Zhi-Yuan; Takakura, Nobuyuki, E-mail: ntakaku@biken.osaka-u.ac.jp

2015-06-10

Hematopoietic stem cells (HSCs) can survive long-term in a state of dormancy. Little is known about how histone deacetylase inhibitors (HDACi) affect HSC kinetics. Here, we use trichostatin A (TSA), a histone deacetylase inhibitor, to enforce histone acetylation and show that this suppresses cell cycle entry by dormant HSCs. Previously, we found that haploinsufficiency of PSF1, a DNA replication factor, led to attenuation of the bone marrow (BM) HSC pool size and lack of acute proliferation after 5-FU ablation. Because PSF1 protein is present in CD34{sup +} transiently amplifying HSCs but not in CD34{sup −} long-term reconstituting-HSCs which are restingmore » in a dormant state, we analyzed the relationship between dormancy and PSF1 expression, and how a histone deacetylase inhibitor affects this. We found that CD34{sup +} HSCs produce long functional PSF1 (PSF1a) but CD34{sup −} HSCs produce a shorter possibly non-functional PSF1 (PSF1b, c, dominantly PSF1c). Using PSF1a-overexpressing NIH-3T3 cells in which the endogenous PSF1 promoter is suppressed, we found that TSA treatment promotes production of the shorter form of PSF1 possibly by inducing recruitment of E2F family factors upstream of the PSF1 transcription start site. Our data document one mechanism by which histone deacetylase inhibitors affect the dormancy of HSCs by regulating the DNA replication factor PSF1. - Highlights: • Hematopoetic stem cell dormancy is controlled by histone deacetylation inhibitors. • Dormancy of HSCs is associated with a shorter form of non-functional PSF1. • Histone deacetylase inhibitors suppress PSF1 promoter activity.« less

Duration of sleep inertia after napping during simulated night work and in extended operations.

PubMed

Signal, Tracey Leigh; van den Berg, Margo J; Mulrine, Hannah M; Gander, Philippa H

2012-07-01

Due to the mixed findings of previous studies, it is still difficult to provide guidance on how to best manage sleep inertia after waking from naps in operational settings. One of the few factors that can be manipulated is the duration of the nap opportunity. The aim of the present study was to investigate the magnitude and time course of sleep inertia after waking from short (20-, 40- or 60-min) naps during simulated night work and extended operations. In addition, the effect of sleep stage on awakening and duration of slow wave sleep (SWS) on sleep inertia was assessed. Two within-subject protocols were conducted in a controlled laboratory setting. Twenty-four healthy young men (Protocol 1: n = 12, mean age = 25.1 yrs; Protocol 2: n = 12, mean age = 23.2 yrs) were provided with nap opportunities of 20-, 40-, and 60-min (and a control condition of no nap) ending at 02:00 h after ∼20 h of wakefulness (Protocol 1 [P1]: simulated night work) or ending at 12:00 h after ∼30 h of wakefulness (Protocol 2 [P2]: simulated extended operations). A 6-min test battery, including the Karolinska Sleepiness Scale (KSS) and the 4-min 2-Back Working Memory Task (WMT), was repeated every 15 min the first hour after waking. Nap sleep was recorded polysomnographically, and in all nap opportunities sleep onset latency was short and sleep efficiency high. Mixed-model analyses of variance (ANOVA) for repeated measures were calculated and included the factors time (time post-nap), nap opportunity (duration of nap provided), order (order in which the four protocols were completed), and the interaction of these terms. Results showed no test x nap opportunity effect (i.e., no effect of sleep inertia) on KSS. However, WMT performance was impaired (slower reaction time, fewer correct responses, and increased omissions) on the first test post-nap, primarily after a 40- or 60-min nap. In P2 only, performance improvement was evident 45 min post-awakening for naps of 40 min or more. In ANOVAs

Spotlight on daytime napping during early childhood.

PubMed

Horváth, Klára; Plunkett, Kim

2018-01-01

Daytime napping undergoes a remarkable change in early childhood, and research regarding its relationship to cognitive development has recently accelerated. In this review, we summarize our current understanding of this relationship focusing on children aged <5 years. First, we evaluate different studies on the basis of the experimental design used and the specific cognitive processes they investigate. Second, we analyze how the napping status of children may modulate the relationship between learning and napping. Third, the possible role of sleep spindles, ie, specific electroencephalographic components during sleep, in cognitive development is explored. We conclude that daytime napping is crucial in early memory development.

Using a model comparison approach to describe the assembly pathway for histone H1

PubMed Central

Contreras, Carlos; Villasana, Minaya; Hendzel, Michael J.

2018-01-01

Histones H1 or linker histones are highly dynamic proteins that diffuse throughout the cell nucleus and associate with chromatin (DNA and associated proteins). This binding interaction of histone H1 with the chromatin is thought to regulate chromatin organization and DNA accessibility to transcription factors and has been proven to involve a kinetic process characterized by a population that associates weakly with chromatin and rapidly dissociates and another population that resides at a binding site for up to several minutes before dissociating. When considering differences between these two classes of interactions in a mathematical model for the purpose of describing and quantifying the dynamics of histone H1, it becomes apparent that there could be several assembly pathways that explain the kinetic data obtained in living cells. In this work, we model these different pathways using systems of reaction-diffusion equations and carry out a model comparison analysis using FRAP (fluorescence recovery after photobleaching) experimental data from different histone H1 variants to determine the most feasible mechanism to explain histone H1 binding to chromatin. The analysis favors four different chromatin assembly pathways for histone H1 which share common features and provide meaningful biological information on histone H1 dynamics. We show, using perturbation analysis, that the explicit consideration of high- and low-affinity associations of histone H1 with chromatin in the favored assembly pathways improves the interpretation of histone H1 experimental FRAP data. To illustrate the results, we use one of the favored models to assess the kinetic changes of histone H1 after core histone hyperacetylation, and conclude that this post-transcriptional modification does not affect significantly the transition of histone H1 from a weakly bound state to a tightly bound state. PMID:29352283

Cytokine Polymorphisms are Associated with Daytime Napping in Adults Living with HIV

PubMed Central

Byun, Eeeseung; Gay, Caryl L.; Portillo, Carmen J.; Pullinger, Clive R.; Aouizerat, Bradley E.; Lee, Kathryn A.

2017-01-01

Objective/Background Daytime napping longer than one hour has been associated with an increased risk for all-cause mortality. Associations between cytokine polymorphisms and daytime napping in chronic illnesses such as HIV, however, have not been well described. The purpose of this study was to examine cytokine polymorphisms associated with long daytime napping in adults living with HIV. Methods A cross-sectional analysis was conducted using a convenience sample of 257 adults living with HIV. Daytime napping was assessed with wrist actigraphy data collected over three days. Participants categorized as long nappers (≥ 60 min) were compared to short nappers and non-nappers (< 60 min). Single nucleotide polymorphisms (SNPs) for 15 candidate genes involved in cytokine signaling were analyzed. Genes included: interferon-gamma (IFNG), IFNG receptor 1 (IFNGR1), interleukins (IL1B, IL1R, IL1R2, IL2, IL4, IL6, IL8, IL10, IL13, IL17A), nuclear factors of kappa light polypeptide gene enhancer in B cells (NFKB1 and NFKB2), and tumor necrosis factor alpha (TNFA). Results After adjusting for relevant demographic and clinical characteristics, long daytime napping was associated with 12 SNPs from seven genes: 1) IFNG rs2069728; 2) IL1B rs1143642, rs1143627, and rs16944; 3) IL2 rs2069763; 4) IL6 rs4719714, rs1554606, and rs2069845; 5) IL17A rs3819024 and rs8193036; 6) NFKB1 rs4648110; and 7) NFKB2 rs1056890. Conclusions Cytokine genetic variations may have a role in physiological regulation of daytime napping as well as nocturnal sleep. Cytokine polymorphisms associated with long daytime napping could help identify adults with HIV who may benefit from targeted therapeutic interventions. PMID:28366330

Cytokine polymorphisms are associated with daytime napping in adults living with HIV.

PubMed

Byun, Eeeseung; Gay, Caryl L; Portillo, Carmen J; Pullinger, Clive R; Aouizerat, Bradley E; Lee, Kathryn A

2017-04-01

Daytime napping longer than one hour has been associated with an increased risk for all-cause mortality. Associations between cytokine polymorphisms and daytime napping in chronic illnesses such as HIV, however, have not been well described. The purpose of this study was to examine cytokine polymorphisms associated with long daytime napping in adults living with HIV. A cross-sectional analysis was conducted using a convenience sample of 257 adults living with HIV. Daytime napping was assessed with wrist actigraphy data collected over three days. Participants categorized as long nappers (≥60 min) were compared to short nappers and non-nappers (<60 min). Single nucleotide polymorphisms (SNPs) for 15 candidate genes involved in cytokine signaling were analyzed. Genes included: interferon-gamma (IFNG), IFNG receptor 1 (IFNGR1), interleukins (IL1B, IL1R, IL1R2, IL2, IL4, IL6, IL8, IL10, IL13, IL17A), nuclear factors of kappa light polypeptide gene enhancer in B cells (NFKB1 and NFKB2), and tumor necrosis factor alpha (TNFA). After adjusting for relevant demographic and clinical characteristics, long daytime napping was associated with 12 SNPs from seven genes: 1) IFNG rs2069728; 2) IL1B rs1143642, rs1143627, and rs16944; 3) IL2 rs2069763; 4) IL6 rs4719714, rs1554606, and rs2069845; 5) IL17A rs3819024 and rs8193036; 6) NFKB1 rs4648110; and 7) NFKB2 rs1056890. Cytokine genetic variations may have a role in physiological regulation of daytime napping as well as nocturnal sleep. Cytokine polymorphisms associated with long daytime napping could help identify adults with HIV who may benefit from targeted therapeutic interventions. Copyright © 2017 Elsevier B.V. All rights reserved.

Sleep spindles in midday naps enhance learning in preschool children

PubMed Central

Kurdziel, Laura; Duclos, Kasey; Spencer, Rebecca M. C.

2013-01-01

Despite the fact that midday naps are characteristic of early childhood, very little is understood about the structure and function of these sleep bouts. Given that sleep benefits memory in young adults, it is possible that naps serve a similar function for young children. However, children transition from biphasic to monophasic sleep patterns in early childhood, eliminating the nap from their daily sleep schedule. As such, naps may contain mostly light sleep stages and serve little function for learning and memory during this transitional age. Lacking scientific understanding of the function of naps in early childhood, policy makers may eliminate preschool classroom nap opportunities due to increasing curriculum demands. Here we show evidence that classroom naps support learning in preschool children by enhancing memories acquired earlier in the day compared with equivalent intervals spent awake. This nap benefit is greatest for children who nap habitually, regardless of age. Performance losses when nap-deprived are not recovered during subsequent overnight sleep. Physiological recordings of naps support a role of sleep spindles in memory performance. These results suggest that distributed sleep is critical in early learning; when short-term memory stores are limited, memory consolidation must take place frequently. PMID:24062429

Sleep spindles in midday naps enhance learning in preschool children.

PubMed

Kurdziel, Laura; Duclos, Kasey; Spencer, Rebecca M C

2013-10-22

Despite the fact that midday naps are characteristic of early childhood, very little is understood about the structure and function of these sleep bouts. Given that sleep benefits memory in young adults, it is possible that naps serve a similar function for young children. However, children transition from biphasic to monophasic sleep patterns in early childhood, eliminating the nap from their daily sleep schedule. As such, naps may contain mostly light sleep stages and serve little function for learning and memory during this transitional age. Lacking scientific understanding of the function of naps in early childhood, policy makers may eliminate preschool classroom nap opportunities due to increasing curriculum demands. Here we show evidence that classroom naps support learning in preschool children by enhancing memories acquired earlier in the day compared with equivalent intervals spent awake. This nap benefit is greatest for children who nap habitually, regardless of age. Performance losses when nap-deprived are not recovered during subsequent overnight sleep. Physiological recordings of naps support a role of sleep spindles in memory performance. These results suggest that distributed sleep is critical in early learning; when short-term memory stores are limited, memory consolidation must take place frequently.

Alertness management in flight operations - Strategic napping

NASA Technical Reports Server (NTRS)

Rosekind, Mark R.; Gander, Philippa H.; Dinges, David F.

1991-01-01

Strategic napping in two different flight operation environments is considered to illustrate its application as a fatigue countermeasure. Data obtained from commercial short-haul and long-haul operations demonstrated the utility and current practices of strategic napping. A preplanned cockpit nap acted as an acute 'safety valve' for the sleep loss, circadian disruption, and fatigue that occurs in long-haul flying.

Day Napping and Short Night Sleeping Are Associated With Higher Risk of Diabetes in Older Adults

PubMed Central

Xu, Qun; Song, Yiqing; Hollenbeck, Albert; Blair, Aaron; Schatzkin, Arthur; Chen, Honglei

2010-01-01

OBJECTIVE To examine whether day napping or short night sleeping is associated with higher risk of diabetes. RESEARCH DESIGN AND METHODS This was a prospective study of hours of day napping and night sleeping assessed in 1996–1997 in relation to diabetes diagnosed between 2000 and 2006 (n = 10,143) among 174,542 participants in the National Institutes of Health (NIH)-AARP Diet and Health Study. Odds ratios (ORs) and 95% CI were derived from multivariate logistic regression models. RESULTS Longer day napping was associated with a higher risk of diabetes. After adjustment for potential confounders, ORs were 1.23 (95% CI 1.18–1.29) for those reporting <1 h and 1.55 (95% CI 1.45–1.66) for those reporting ≥1 h of napping compared with individuals who did not nap (Ptrend < 0.0001). For night sleeping, with 7–8 h as the referent, the OR was 1.46 (95% CI 1.31–1.63) for <5 h, 1.11 (1.06–1.16) for 5–6 h, and 1.11 (0.99–1.24) for ≥9 h. In both analyses, additional adjustment for BMI only modestly attenuated the associations. Further analysis showed a statistically significant interaction between hours of napping and sleeping on diabetes (Pinteraction < 0.0001). Among participants with no napping, only short night sleeping was associated with higher occurrence of diabetes, whereas among those with ≥1 h of napping, both long and short sleeping was associated with higher risk. CONCLUSIONS Day napping and short night sleeping are associated with higher risk of diabetes. The association between sleep duration and diabetes may be modified by napping habit. PMID:19825823

Spotlight on daytime napping during early childhood

PubMed Central

Horváth, Klára; Plunkett, Kim

2018-01-01

Daytime napping undergoes a remarkable change in early childhood, and research regarding its relationship to cognitive development has recently accelerated. In this review, we summarize our current understanding of this relationship focusing on children aged <5 years. First, we evaluate different studies on the basis of the experimental design used and the specific cognitive processes they investigate. Second, we analyze how the napping status of children may modulate the relationship between learning and napping. Third, the possible role of sleep spindles, ie, specific electroencephalographic components during sleep, in cognitive development is explored. We conclude that daytime napping is crucial in early memory development. PMID:29576733

Abundance of intrinsic structural disorder in the histone H1 subtypes.

PubMed

Kowalski, Andrzej

2015-12-01

The intrinsically disordered proteins consist of partially structured regions linked to the unstructured stretches, which consequently form the transient and dynamic conformational ensembles. They undergo disorder to order transition upon binding their partners. Intrinsic disorder is attributed to histones H1, perceived as assemblers of chromatin structure and the regulators of DNA and proteins activity. In this work, the comparison of intrinsic disorder abundance in the histone H1 subtypes was performed both by the analysis of their amino acid composition and by the prediction of disordered stretches, as well as by identifying molecular recognition features (MoRFs) and ANCHOR protein binding regions (APBR) that are responsible for recognition and binding. Both human and model organisms-animals, plants, fungi and protists-have H1 histone subtypes with the properties typical of disordered state. They possess a significantly higher content of hydrophilic and charged amino acid residues, arranged in the long regions, covering over half of the whole amino acid residues in chain. Almost complete disorder corresponds to histone H1 terminal domains, including MoRFs and ANCHOR. Those motifs were also identified in a more ordered histone H1 globular domain. Compared to the control (globular and fibrous) proteins, H1 histones demonstrate the increased folding rate and a higher proportion of low-complexity segments. The results of this work indicate that intrinsic disorder is an inherent structural property of histone H1 subtypes and it is essential for establishing a protein conformation which defines functional outcomes affecting on DNA- and/or partner protein-dependent cell processes. Copyright © 2015 Elsevier Ltd. All rights reserved.

The histone modifications governing TFF1 transcription mediated by estrogen receptor.

PubMed

Li, Yanyan; Sun, Luyang; Zhang, Yu; Wang, Dandan; Wang, Feng; Liang, Jing; Gui, Bin; Shang, Yongfeng

2011-04-22

Transcription regulation by histone modifications is a major contributing factor to the structural and functional diversity in biology. These modifications are encrypted as histone codes or histone languages and function to establish and maintain heritable epigenetic codes that define the identity and the fate of the cell. Despite recent advances revealing numerous histone modifications associated with transcription regulation, how such modifications dictate the process of transcription is not fully understood. Here we describe spatial and temporal analyses of the histone modifications that are introduced during estrogen receptor α (ERα)-activated transcription. We demonstrated that aborting RNA polymerase II caused a disruption of the histone modifications that are associated with transcription elongation but had a minimal effect on modifications deposited during transcription initiation. We also found that the histone H3S10 phosphorylation mark is catalyzed by mitogen- and stress-activated protein kinase 1 (MSK1) and is recognized by a 14-3-3ζ/14-3-3ε heterodimer through its interaction with H3K4 trimethyltransferase SMYD3 and the p52 subunit of TFIIH. We showed that H3S10 phosphorylation is a prerequisite for H3K4 trimethylation. In addition, we demonstrated that SET8/PR-Set7/KMT5A is required for ERα-regulated transcription and its catalyzed H4K20 monomethylation is implicated in both transcription initiation and elongation. Our experiments provide a relatively comprehensive analysis of histone modifications associated with ERα-regulated transcription and define the biological meaning of several key components of the histone code that governs ERα-regulated transcription.

Napping in college students and its relationship with nighttime sleep.

PubMed

Ye, Lichuan; Hutton Johnson, Stacy; Keane, Kathleen; Manasia, Michael; Gregas, Matt

2015-01-01

Abstract. To examine the habit of napping and its relationship with nighttime sleep in college students. Four hundred and forty undergraduate students who responded to an anonymous online survey in April 2010. Three questions were asked to determine the frequency, length, and timing of napping during the past month. Sleep quality was measured by the Pittsburgh Sleep Quality Index (PSQI). The PSQI score significantly differed among self-reported nap-frequency (p=.047) and nap-length (p=.017) groups, with those who napped more than 3 times per week and those who napped more than 2 hours having the poorest sleep quality. Students who napped between 6 and 9 pm had shorter sleep on school nights compared with students in other nap-timing groups (p=.002). College students who are self-reported frequent, long, and late nappers may have a higher risk of poor nighttime sleep quality and more severe sleep deprivation.

Sex difference in the association between habitual daytime napping and prevalence of diabetes: a population-based study.

PubMed

Sun, Kan; Li, Feng; Qi, Yiqin; Lin, Diaozhu; Ren, Meng; Xu, Mingtong; Li, Fangping; Li, Yan; Yan, Li

2016-05-01

Our objective was to evaluate the associations between habitual daytime napping and diabetes and whether it varies by sex, menopause, and sleep quality. We conducted a population-based cross-sectional study in 8621 eligible individuals aged 40 years or older. Information on daytime napping hours, night-time sleep duration, history of menstruation, and sleep quality was self-reported. Diabetes was diagnosed according to the 1999 World Health Organization diagnostic criteria. The prevalence of diabetes was 19.4 % in men and 15.6 % in women. Increased daytime napping hours were positively associated with parameters of glycometabolism in women, such as fasting plasma glucose, oral glucose tolerance test (OGTT) 2-h plasma glucose, and Hemoglobin A1c (HbA1c, all P for trend <0.05). In women, the prevalence of diabetes in no-habitual daytime napping group, 0-1-h daytime napping group, and more than 1-h daytime napping group were 14.5, 15.6, and 20.8 %, respectively (P for trend = 0.0004). A similar trend was detected in postmenopausal women (P for trend = 0.002). In multivariate logistic regression analysis, compared with no-habitual daytime napping postmenopausal women, those with daytime napping more than 1 h had higher prevalent diabetes (odds ratios 1.36, 95 % confidence interval, 1.04-1.77). In subgroup analysis of postmenopausal women, associations of daytime napping levels and prevalent diabetes were detected in older, overweight participants with good sleep quality who have not retired from work. In conclusion, our study suggests that habitual daytime napping is associated with prevalence of diabetes in postmenopausal women.

Napping reduces emotional attention bias during early childhood.

PubMed

Cremone, Amanda; Kurdziel, Laura B F; Fraticelli-Torres, Ada; McDermott, Jennifer M; Spencer, Rebecca M C

2017-07-01

Sleep loss alters processing of emotional stimuli in preschool-aged children. However, the mechanism by which sleep modifies emotional processing in early childhood is unknown. We tested the hypothesis that a nap, compared to an equivalent time spent awake, reduces biases in attention allocation to affective information. Children (n = 43; M = 55.40 months, SD = 8.05 months) completed a Dot Probe task, which provides a measure of attention biases to emotional stimuli, following a mid-day nap and an equivalent interval spent awake. No emotional attention biases emerged when children napped. However, when nap-deprived, children exhibited biases towards negative and positive stimuli. This emotional bias after wake was greater in children who napped habitually. Gender differences also emerged such that females were more attentive to positive emotional stimuli whereas males showed heightened attention to negative emotional stimuli, regardless of having napped or not. Moreover, greater slow wave activity (SWA) during the nap was associated with faster responding, which suggests that SWA may promote efficiency of attention allocation. A video abstract of this article can be viewed at: https://www.youtube.com/watch?v=JIoZ8mzxQgg. © 2016 John Wiley & Sons Ltd.

Effects of napping on neuromuscular fatigue in myasthenia gravis.

PubMed

Kassardjian, Charles D; Murray, Brian J; Kokokyi, Seint; Jewell, Dana; Barnett, Carolina; Bril, Vera; Katzberg, Hans D

2013-11-01

The relationship between sleep and neuromuscular fatigue is understood poorly. The goal of this study was to evaluate the effects of napping on quantitative measures of neuromuscular fatigue in patients with myasthenia gravis (MG). Eight patients with mild to moderate MG were recruited. Patients underwent maintenance of wakefulness tests (MWT) and multiple sleep latency tests (MSLT). The Quantitative Myasthenia Gravis Score (QMGS) was measured before nap and after each nap to examine the effects of napping and sleep on neuromuscular weakness. Results showed that QMGS improves only after naps where patients slept more than 5 min but not where patients did not sleep or slept less than 5 min. Daytime napping mitigates neuromuscular fatigue in patients with MG, especially if patients slept for more than 5 min. Copyright © 2013 Wiley Periodicals, Inc.

A Daytime Nap Facilitates Generalization of Word Meanings in Young Toddlers

PubMed Central

Horváth, Klára; Liu, Siying; Plunkett, Kim

2016-01-01

Study Objectives: One of the key processes in language development is generalization—the selection and extension of relevant features and information to similar objects and concepts. Little is known about how sleep influences generalization, and studies on the topic are inconclusive. Our aim was to investigate how a nap affects generalization in 16-mo-olds. We hypothesized that a nap is necessary for successful generalization of word meanings. Methods: Twenty-eight 16-mo-old, typically developing toddlers were randomly assigned to nap and wake groups. We trained toddlers with two novel object-word pairs and tested their initial ability to generalize. Toddlers took part in an intermodal preferential looking task, in which they were shown different colored versions of the original objects and heard one of the trained labels. If toddlers understand the label, they are expected to increase their looking time to the target. Looking behavior was measured with an automated eye tracker. Afterward, the nap group went to sleep, while the wake group stayed awake for approximately 2 h. We then repeated the test of their performance on the generalization task. Results: A significant interaction of group and session was found in preferential looking. The performance of the nap group increased after the nap, whereas that of the wake group did not change. Conclusions: Our results suggest that napping improves generalization in toddlers. Citation: Horváth K, Liu S, Plunkett K. A daytime nap facilitates generalization of word meanings in young toddlers. SLEEP 2016;39(1):203–207. PMID:26237777

A NAP-AAO3 Regulatory Module Promotes Chlorophyll Degradation via ABA Biosynthesis in Arabidopsis Leaves[W][OPEN

PubMed Central

Yang, Jiading; Worley, Eric

2014-01-01

Chlorophyll degradation is an important part of leaf senescence, but the underlying regulatory mechanisms are largely unknown. Excised leaves of an Arabidopsis thaliana NAC-LIKE, ACTIVATED BY AP3/PI (NAP) transcription factor mutant (nap) exhibited lower transcript levels of known chlorophyll degradation genes, STAY-GREEN1 (SGR1), NON-YELLOW COLORING1 (NYC1), PHEOPHYTINASE (PPH), and PHEIDE a OXYGENASE (PaO), and higher chlorophyll retention than the wild type during dark-induced senescence. Transcriptome coexpression analysis revealed that abscisic acid (ABA) metabolism/signaling genes were disproportionately represented among those positively correlated with NAP expression. ABA levels were abnormally low in nap leaves during extended darkness. The ABA biosynthetic genes 9-CIS-EPOXYCAROTENOID DIOXYGENASE2, ABA DEFICIENT3, and ABSCISIC ALDEHYDE OXIDASE3 (AAO3) exhibited abnormally low transcript levels in dark-treated nap leaves. NAP transactivated the promoter of AAO3 in mesophyll cell protoplasts, and electrophoretic mobility shift assays showed that NAP can bind directly to a segment (−196 to −162 relative to the ATG start codon) of the AAO3 promoter. Exogenous application of ABA increased the transcript levels of SGR1, NYC1, PPH, and PaO and suppressed the stay-green phenotype of nap leaves during extended darkness. Overexpression of AAO3 in nap leaves also suppressed the stay-green phenotype under extended darkness. Collectively, the results show that NAP promotes chlorophyll degradation by enhancing transcription of AAO3, which leads to increased levels of the senescence-inducing hormone ABA. PMID:25516602

Napping during the night shift and recovery after work among hospital nurses1

PubMed Central

Palermo, Thaís Aparecida de Castro; Rotenberg, Lúcia; Zeitoune, Regina Célia Gollner; Silva-Costa, Aline; Souto, Ester Paiva; Griep, Rosane Härter

2015-01-01

OBJECTIVE: To analyze the association between the length of napping during the night shift and the recovery after work among nurses. METHOD: Cross-sectional epidemiological study involving 1940 nurses from 18 public hospitals in the City of Rio de Janeiro. A multidimensional and self-applied questionnaire was used with information about health, sociodemographic and occupational characteristics, health-related behaviors and housework. Multiple logistic regression was applied to identify the association, adjusted for confounding variables. RESULTS: The gross analyses showed 44%, 127% and 66% higher chances of a high level of recovery after work for nurses who sleep up to two hours, between 2.1 and 3 hours and 3.1 hours or more, respectively, when compared to the nurses who do not sleep. After adjusting for confounding variables, the association only continues significant for the group that sleeps 2.1 to 3 hours during the night shift (OR=1.79; 95%CI=1.33-2.41). CONCLUSION: The association between the length of napping and the high level of recovery after work, confirmed in the present results, can be included in the studies that aim to support more appropriate policies aimed at improving the workers' work, life and health conditions, not only in nursing, but night-shift workers in general. PMID:25806639

Napping is associated with increased risk of type 2 diabetes: the Guangzhou Biobank Cohort Study.

PubMed

Lam, Kin-Bong Hubert; Jiang, Chao Qiang; Thomas, G Neil; Arora, Teresa; Zhang, Wei Sen; Taheri, Shahrad; Adab, Peymané; Lam, Tai Hing; Cheng, Kar Keung

2010-03-01

Intentional napping is very common, particularly in China. However, there are limited data regarding its potential health effects. We therefore examined the possible relationship between napping and type 2 diabetes. Cross-sectional analysis of baseline data from the Guangzhou Biobank Cohort Study. Community-based elderly association in Guangzhou, China. 19,567 Chinese men and women aged 50 years or older. Self-reported frequency of napping was obtained by questionnaire and type 2 diabetes was assessed by fasting blood glucose and/or self-reports of physician diagnosis or treatment. Participants reporting frequent naps (4-6 days/week and daily) were 42% to 52% more likely to have diabetes. The relationships remained essentially unchanged after adjustments were made for demographics, lifestyle and sleep habits, health status, adiposity, and metabolic markers (odds ratio for diabetes 1.36 [95% CI 1.17-1.57] in 4-6 days/week, 1.28 [1.15-1.44] in daily nappers). Similar associations were found between napping and impaired fasting glucose. Removal of those with potential ill health and daytime sleepiness did not alter the observed associations. Napping is associated with elevated prevalence of diabetes and impaired fasting glucose in this older Chinese sample. Our finding suggests that it is less likely that diabetes leads to daytime sleepiness. This raises the possibility that napping may increase the risk of diabetes. Confirmation by longitudinal studies is needed.

[Association between insomnia symptoms, daytime napping, and falls in community-dwelling elderly].

PubMed

Pereira, Alexandre Alves; Ceolim, Maria Filomena; Neri, Anita Liberalesso

2013-03-01

This study focused on associations between insomnia symptoms, daytime napping, and falls in community-dwelling elderly, using a population-based cross-sectional design and probability sample with 689 community-dwelling elders. The protocol consisted of self-reported and physical performance variables. The study used univariate and multivariate logistic regression analysis with statistical significance set at p < 0.05. Prevalence rates for insomnia symptoms and daytime napping were 49.9% (n = 339) and 62.8% (n = 432), respectively. 14.4% reported a single fall and 11.9% reported multiple falls. Falls were associated with female gender (OR = 7.73; 95%CI: 3.03-19.72), age > 80 (OR = 3.48; 95%CI: 1.54-7.85), napping (OR = 2.24; 95%CI: 1.24-4.05), and depressive symptoms (OR = 1.98; 95%CI: 1.11-3.53). The association between daytime napping and falls corroborates data from international research. Identifying modifiable risk factors may help programs to prevent falls in the elderly.

The histone chaperone TAF-I/SET/INHAT is required for transcription in vitro of chromatin templates.

PubMed

Gamble, Matthew J; Erdjument-Bromage, Hediye; Tempst, Paul; Freedman, Leonard P; Fisher, Robert P

2005-01-01

To uncover factors required for transcription by RNA polymerase II on chromatin, we fractionated a mammalian cell nuclear extract. We identified the histone chaperone TAF-I (also known as INHAT [inhibitor of histone acetyltransferase]), which was previously proposed to repress transcription, as a potent activator of chromatin transcription responsive to the vitamin D3 receptor or to Gal4-VP16. TAF-I associates with chromatin in vitro and can substitute for the related protein NAP-1 in assembling chromatin onto cloned DNA templates in cooperation with the remodeling enzyme ATP-dependent chromatin assembly factor (ACF). The chromatin assembly and transcriptional activation functions are distinct, however, and can be dissociated temporally. Efficient transcription of chromatin assembled with TAF-I still requires the presence of TAF-I during the polymerization reaction. Conversely, TAF-I cannot stimulate transcript elongation when added after the other factors necessary for assembly of a preinitiation complex on naked DNA. Thus, TAF-I is required to facilitate transcription at a step after chromatin assembly but before transcript elongation.

Relationships Among Daytime Napping and Fatigue, Sleep Quality, and Quality of Life in Cancer Patients.

PubMed

Sun, Jia-Ling; Lin, Chia-Chin

2016-01-01

The relationships among napping and sleep quality, fatigue, and quality of life (QOL) in cancer patients are not clearly understood. The aim of the study was to determine whether daytime napping is associated with nighttime sleep, fatigue, and QOL in cancer patients. In total, 187 cancer patients were recruited. Daytime napping, nighttime self-reported sleep, fatigue, and QOL were assessed using a questionnaire. Objective sleep parameters were collected using a wrist actigraph. According to waking-after-sleep-onset measurements, patients who napped during the day experienced poorer nighttime sleep than did patients who did not (t = -2.44, P = .02). Daytime napping duration was significantly negatively correlated with QOL. Patients who napped after 4 PM had poorer sleep quality (t = -1.93, P = .05) and a poorer Short-Form Health Survey mental component score (t = 2.06, P = .04) than did patients who did not. Fatigue, daytime napping duration, and sleep quality were significant predictors of the mental component score and physical component score, accounting for 45.7% and 39.3% of the variance, respectively. Daytime napping duration was negatively associated with QOL. Napping should be avoided after 4 PM. Daytime napping affects the QOL of cancer patients. Future research can determine the role of napping in the sleep hygiene of cancer patients.

Associations between longer habitual day napping and non-alcoholic fatty liver disease in an elderly Chinese population.

PubMed

Qu, Hua; Wang, Hang; Deng, Min; Wei, Huili; Deng, Huacong

2014-01-01

Both longer habitual day napping and Non-Alcoholic Fatty Liver Disease (NAFLD) are associated with diabetes and inflammation, but the association between day napping and NAFLD remains unexplored. To investigate the association between the duration of habitual day napping and NAFLD in an elderly Chinese population and to gain insight into the role of inflammatory cytokines in this association. We conducted a series of cross-sectional studies of the community population in Chongqing, China, from 2011 to 2012. Among 6998 participants aged 40 to 75 years, 6438 eligible participants were included in the first study and analyzed to observe the association between day napping duration and NAFLD. In a separate study, 80 non-nappers and 90 nappers were selected to identify the role of inflammatory cytokines in this association. Logistic regression models were used to examine the odds ratios (ORs) of day nap duration with NAFLD. Day nappers had a significantly higher prevalence of NAFLD (P<0.001). Longer day napping duration was associated in a dose-dependent manner with NAFLD (P trend <0.001). After adjustment for potential confounders, the ORs were 1.67 (95% CI 1.13-2.46) for those reporting 0.5-1 h and 1.49 (95% CI 1.01-2.19) for those reporting >1 h of day napping compared with individuals who did not take day naps (all P<0.05). Longer-duration day nappers had higher levels of IL-6 and progranulin (PGRN) but lower levels of Secreted frizzled-related protein-5 (SFRP5, all P trend <0.001). After adjusting for IL-6, PGRN, and SFRP5, the association between day napping duration and NAFLD disappeared (all P>0.05). Longer day napping duration is associated with a higher prevalence of NAFLD, and inflammatory cytokines may be an essential link between day napping and NAFLD.

Longtime napping is associated with cardiovascular risk estimation according to Framingham risk score in postmenopausal women.

PubMed

Li, Feng; Sun, Kan; Lin, Diaozhu; Qi, Yiqin; Li, Yan; Yan, Li; Ren, Meng

2016-09-01

Menopause can affect the physiological timing system, which could result in circadian rhythm changes and development of napping habits. Whether longtime napping in postmenopausal women is associated with cardiovascular disease is, however, still debated. The present study aims to investigate this association. We conducted a population-based study in 4,616 postmenopausal Chinese women. Information on sleep duration was self-reported. The Framingham General Cardiovascular Risk Score was calculated and used to identify participants at high risk of coronary heart disease (CHD). Increased daytime napping hours were positively associated with cardiovascular disease risk factors in postmenopausal women, such as age, waist circumference, systolic blood pressure, triglycerides, fasting glucose, postload glucose, and hemoglobin A1C (all P for trend <0.05). The prevalence of high risk of CHD increased with daytime napping hours, and was 3.7%, 4.3%, and 6.9% in the no daytime napping group, the 0.1 to 1 hour group, and the more than 1 hour group, respectively (P for trend = 0.005). Compared with the no daytime napping group, postmenopausal women with daytime napping more than 1 hour had higher risk of CHD in both univariate (odds ratio 1.94, 95% CI, 1.29-2.95) and multivariate (odds ratio 1.61, 95% CI, 1.03-2.52) logistic regression analyses. No statistically significant association was detected between night sleeping hours and high risk of CHD in postmenopausal participants. Daytime napping is positively associated with estimated 10-year CHD risk in postmenopausal Chinese women.

Structural analysis of the core COMPASS family of histone H3K4 methylases from yeast to human

PubMed Central

Takahashi, Yoh-hei; Westfield, Gerwin H.; Oleskie, Austin N.; Trievel, Raymond C.; Shilatifard, Ali; Skiniotis, Georgios

2011-01-01

Histone H3 lysine 4 (H3K4) methylation is catalyzed by the highly evolutionarily conserved multiprotein complex known as Set1/COMPASS or MLL/COMPASS-like complexes from yeast to human, respectively. Here we have reconstituted fully functional yeast Set1/COMPASS and human MLL/COMPASS-like complex in vitro and have identified the minimum subunit composition required for histone H3K4 methylation. These subunits include the methyltransferase C-terminal SET domain of Set1/MLL, Cps60/Ash2L, Cps50/RbBP5, Cps30/WDR5, and Cps25/Dpy30, which are all common components of the COMPASS family from yeast to human. Three-dimensional (3D) cryo-EM reconstructions of the core yeast complex, combined with immunolabeling and two-dimensional (2D) EM analysis of the individual subcomplexes reveal a Y-shaped architecture with Cps50 and Cps30 localizing on the top two adjacent lobes and Cps60-Cps25 forming the base at the bottom. EM analysis of the human complex reveals a striking similarity to its yeast counterpart, suggesting a common subunit organization. The SET domain of Set1 is located at the juncture of Cps50, Cps30, and the Cps60-Cps25 module, lining the walls of a central channel that may act as the platform for catalysis and regulative processing of various degrees of H3K4 methylation. This structural arrangement suggested that COMPASS family members function as exo-methylases, which we have confirmed by in vitro and in vivo studies. PMID:22158900

Structural analysis of the core COMPASS family of histone H3K4 methylases from yeast to human.

PubMed

Takahashi, Yoh-hei; Westfield, Gerwin H; Oleskie, Austin N; Trievel, Raymond C; Shilatifard, Ali; Skiniotis, Georgios

2011-12-20

Histone H3 lysine 4 (H3K4) methylation is catalyzed by the highly evolutionarily conserved multiprotein complex known as Set1/COMPASS or MLL/COMPASS-like complexes from yeast to human, respectively. Here we have reconstituted fully functional yeast Set1/COMPASS and human MLL/COMPASS-like complex in vitro and have identified the minimum subunit composition required for histone H3K4 methylation. These subunits include the methyltransferase C-terminal SET domain of Set1/MLL, Cps60/Ash2L, Cps50/RbBP5, Cps30/WDR5, and Cps25/Dpy30, which are all common components of the COMPASS family from yeast to human. Three-dimensional (3D) cryo-EM reconstructions of the core yeast complex, combined with immunolabeling and two-dimensional (2D) EM analysis of the individual subcomplexes reveal a Y-shaped architecture with Cps50 and Cps30 localizing on the top two adjacent lobes and Cps60-Cps25 forming the base at the bottom. EM analysis of the human complex reveals a striking similarity to its yeast counterpart, suggesting a common subunit organization. The SET domain of Set1 is located at the juncture of Cps50, Cps30, and the Cps60-Cps25 module, lining the walls of a central channel that may act as the platform for catalysis and regulative processing of various degrees of H3K4 methylation. This structural arrangement suggested that COMPASS family members function as exo-methylases, which we have confirmed by in vitro and in vivo studies.

NAP enzyme recruitment in simultaneous bioremediation and nanoparticles synthesis.

PubMed

Eltarahony, Marwa; Zaki, Sahar; Kheiralla, Zeinab; Abd-El-Haleem, Desouky

2018-06-01

The periplasmic nitrate reductase enzyme (NAP) has become attractive catalyst, whose exploitation has emerged as one of the indispensable strategies toward environmentally benign applications. To achieve them efficiently and overcome the sensitivity of NAP in harsh environmental circumstances, the immobilization for denitrifying bacteria and NAP enzyme for simultaneous bioremediation and bionanoparticles synthesis was studied. NAP catalyzed NO 3 - reduction at V max of 0.811 μM/min and K m of 14.02 mM. Concurrently, the immobilized MMT cells completely removed NO 3 - upon 192 h with AgNPs synthesis ranging from 23.26 to 58.14 nm as indicated by SEM. Wherase, immobilized NAP exhibited lower efficiency with 28.6% of NO 3 - elimination within 288 h and large aggregated AgNPs ranging from 94.44 nm to 172.22 nm. To the best of author knowledge, the immobilization for denitrifying bacteria and NAP enzyme for simultaneous bioremediation and bionanoparticles synthesis was not studied before.

Cockpit napping

NASA Technical Reports Server (NTRS)

Graeber, R. Curtis; Rosekind, Mark R.; Connell, Linda J.; Dinges, David F.

1990-01-01

The results of a NASA-sponsored study examining the effectiveness of a brief, preplanned cockpit rest period to improve pilot alertness and performance in nonaugmented long-haul flight operations are discussed. Four regularly scheduled trans-Pacific flight legs were studied. The shortest flight legs were about 7 h and the longest about 9.5 h, with duty periods averaging about 11 h and layovers about 25 h. Three-person B747 crews were divided randomly into two volunteer pilot groups. These crews were nonaugmented, and therefore no relief pilots were available. The rest group, consisting of four crews, was allowed a 40 min opportunity to rest during the overwater cruise portion of the flight. On a preplanned, rotating basis, individual crew members were allowed to nap. It is concluded that a preplanned cockpit nap is associated with significantly better behavioral performance and higher levels of physiological alertness and that this can be accomplished without disrupting normal flight operations or compromising safety.

Temporal Relationships Between Napping and Nocturnal Sleep in Healthy Adolescents.

PubMed

Jakubowski, Karen P; Hall, Martica H; Lee, Laisze; Matthews, Karen A

2017-01-01

Many adolescents do not achieve the recommended 9 hr of sleep per night and report daytime napping, perhaps because it makes up for short nocturnal sleep. This article tests temporal relationships between daytime naps and nighttime sleep as measured by actigraphy and diary among 236 healthy high school students during one school week. Mixed model analyses adjusted for age, race, and gender demonstrated that shorter actigraphy-assessed nocturnal sleep duration predicted longer napping (measured by actigraphy and diary) the next day. Napping (by actigraphy and diary) predicted shorter nocturnal sleep duration and worse sleep efficiency that night measured by actigraphy. Diary-reported napping also predicted poorer self-reported sleep quality that night. Frequent napping may interfere with nocturnal sleep during adolescence.

Differentiation of eosinophilic leukemia EoL-1 cells into eosinophils induced by histone deacetylase inhibitors.

PubMed

Ishihara, Kenji; Takahashi, Aki; Kaneko, Motoko; Sugeno, Hiroki; Hirasawa, Noriyasu; Hong, JangJa; Zee, OkPyo; Ohuchi, Kazuo

2007-03-06

EoL-1 cells differentiate into eosinophils in the presence of n-butyrate, but the mechanism has remained to be elucidated. Because n-butyrate can inhibit histone deacetylases, we hypothesized that the inhibition of histone deacetylases induces the differentiation of EoL-1 cells into eosinophils. In this study, using n-butyrate and two other histone deacetylase inhibitors, apicidin and trichostatin A, we have analyzed the relationship between the inhibition of histone deacetylases and the differentiation into eosinophils in EoL-1 cells. It was demonstrated that apicidin and n-butyrate induced a continuous acetylation of histones H4 and H3, inhibited the proliferation of EoL-1 cells without attenuating the level of FIP1L1-PDGFRA mRNA, and induced the expression of markers for mature eosinophils such as integrin beta7, CCR1, and CCR3 on EoL-1 cells, while trichostatin A evoked a transient acetylation of histones and induced no differentiation into eosinophils. These findings suggest that the continuous inhibition of histone deacetylases in EoL-1 cells induces the differentiation into mature eosinophils.

Self-reported sleep duration and daytime napping are associated with renal hyperfiltration in general population.

PubMed

Lin, Miao; Su, Qing; Wen, Junping; Wei, Shichao; Yao, Jin; Huang, Huibin; Liang, Jixing; Li, Liantao; Lin, Wei; Lin, Lixiang; Lu, Jieli; Bi, Yufang; Wang, Weiqing; Ning, Guang; Chen, Gang

2018-03-01

Renal hyperfiltration (RHF) has emerged as a novel marker of early renal damage in various conditions such as diabetes and metabolic syndrome. Aberrant sleep duration and excessive daytime napping may affect the development of chronic kidney disease (CKD). In this study, the association between sleep duration, daytime napping, and renal hyperfiltration was assessed. This study was conducted in three communities in China. A total of 16,119 community volunteers (5735 males and 10,384 females) aged 40-65 years without CKD were included for the study. Participants with short sleep duration (<6 h/day) or long sleep duration (≥10 h/day) were at a significantly increased risk of renal hyperfiltration. The fully adjusted ORs (95% CI) were 2.112 (1.107, 4.031) and 2.071 (1.504, 2.853), respectively (P < 0.05). In addition, those who took naps longer than 1.5 h per day had a higher risk of renal hyperfiltration compared with those without napping (OR 1.400, 95% CI 1.018-1.924). Further joint analysis indicated that participants with long sleep duration (≥10 h/day) had a more than twofold increased risk of RHF regardless of nap status compared with those who slept 8-9 h per day without daytime napping. The association between sleep duration or daytime napping and RHF could not be explained by the influence of sleep quality. Additional subgroup analysis showed long sleep duration (≥9 h/day) and long daytime napping (≥1.5 h) were associated with an increased risk of RHF among individuals with good sleep quality. Sleep duration less than 6 h/day or more than 10 h/day and long daytime napping tend to be associated with an increased risk of renal hyperfiltration in middle-aged general population, and this relationship was independent of diabetes, hypertension, obesity, or poor sleep quality.

J-curve relation between daytime nap duration and type 2 diabetes or metabolic syndrome: A dose-response meta-analysis

PubMed Central

Yamada, Tomohide; Shojima, Nobuhiro; Yamauchi, Toshimasa; Kadowaki, Takashi

2016-01-01

Adequate sleep is important for good health, but it is not always easy to achieve because of social factors. Daytime napping is widely prevalent around the world. We performed a meta-analysis to investigate the association between napping (or excessive daytime sleepiness: EDS) and the risk of type 2 diabetes or metabolic syndrome, and to quantify the potential dose-response relation using cubic spline models. Electronic databases were searched for articles published up to 2016, with 288,883 Asian and Western subjects. Pooled analysis revealed that a long nap (≥60 min/day) and EDS were each significantly associated with an increased risk of type 2 diabetes versus no nap or no EDS (odds ratio 1.46 (95% CI 1.23–1.74, p < 0.01) for a long nap and 2.00 (1.58–2.53) for EDS). In contrast, a short nap (<60 min/day) was not associated with diabetes (p = 0.75). Dose-response meta-analysis showed a J-curve relation between nap time and the risk of diabetes or metabolic syndrome, with no effect of napping up to about 40 minutes/day, followed by a sharp increase in risk at longer nap times. In summary, longer napping is associated with an increased risk of metabolic disease. Further studies are needed to confirm the benefit of a short nap. PMID:27909305

A Pilot Study to Examine the Relationship Between Napping and Fatigue in Nurses Practicing on the Night Shift.

PubMed

Neville, Kathleen; Velmer, Gillian; Brown, Shari; Robol, Nancy

2017-11-01

The aim of this study is to explore the relationship of night-shift napping on fatigue. Nurses' fatigue, especially at night, interferes with quality of life and job performance and impacts safety and health. Night-shift nurses completed the Brief Fatigue Inventory and a demographic information sheet to determine differences in fatigue between nurses who napped during their night shift as compared with nurses who did not nap. No statistically significant differences in global fatigue were found; differences in rotating shift, age, and, gender were identified. Rotating shifts, a 2nd job, and caring for family predicted fatigue. Based on this pilot study, further investigations of fatigue among night-shift nurses are needed as well as evidence-based support to promote sleep.

Cell cycle-regulated oscillator coordinates core histone gene transcription through histone acetylation

PubMed Central

Kurat, Christoph F.; Lambert, Jean-Philippe; Petschnigg, Julia; Friesen, Helena; Pawson, Tony; Rosebrock, Adam; Gingras, Anne-Claude; Fillingham, Jeffrey; Andrews, Brenda

2014-01-01

DNA replication occurs during the synthetic (S) phase of the eukaryotic cell cycle and features a dramatic induction of histone gene expression for concomitant chromatin assembly. Ectopic production of core histones outside of S phase is toxic, underscoring the critical importance of regulatory pathways that ensure proper expression of histone genes. Several regulators of histone gene expression in the budding yeast Saccharomyces cerevisiae are known, yet the key oscillator responsible for restricting gene expression to S phase has remained elusive. Here, we show that suppressor of Ty (Spt)10, a putative histone acetyltransferase, and its binding partner Spt21 are key determinants of S-phase–specific histone gene expression. We show that Spt21 abundance is restricted to S phase in part by anaphase promoting complex Cdc20-homologue 1 (APCCdh1) and that it is recruited to histone gene promoters in S phase by Spt10. There, Spt21-Spt10 enables the recruitment of a cascade of regulators, including histone chaperones and the histone-acetyltransferase general control nonderepressible (Gcn) 5, which we hypothesize lead to histone acetylation and consequent transcription activation. PMID:25228766

Do night naps impact driving performance and daytime recovery sleep?

PubMed

Centofanti, Stephanie A; Dorrian, Jillian; Hilditch, Cassie J; Banks, Siobhan

2017-02-01

Short, nighttime naps are used as a fatigue countermeasure in night shift work, and may offer protective benefits on the morning commute. However, there is a concern that nighttime napping may impact upon the quality of daytime sleep. The aim of the current project was to investigate the influence of short nighttime naps (<30min) on simulated driving performance and subsequent daytime recovery sleep. Thirty-one healthy subjects (aged 21-35 y; 18 females) participated in a 3-day laboratory study. After a 9-h baseline sleep opportunity (22:00h-07:00h), subjects were kept awake the following night with random assignment to: a 10-min nap ending at 04:00h plus a 10-min nap at 07:00h; a 30-min nap ending at 04:00h; or a no-nap control. A 40-min driving simulator task was administered at 07:00h and 18:30h post-recovery sleep. All conditions had a 6-h daytime recovery sleep opportunity (10:00h-16:00h) the next day. All sleep periods were recorded polysomnographically. Compared to control, the napping conditions did not significantly impact upon simulated driving lane variability, percentage of time in a safe zone, or time to first crash on morning or evening drives (p>0.05). Short nighttime naps did not significantly affect daytime recovery total sleep time (p>0.05). Slow wave sleep (SWS) obtained during the 30-min nighttime nap resulted in a significant reduction in SWS during subsequent daytime recovery sleep (p<0.05), such that the total amount of SWS in 24-h was preserved. Therefore, short naps did not protect against performance decrements during a simulated morning commute, but they also did not adversely affect daytime recovery sleep following a night shift. Further investigation is needed to examine the optimal timing, length or combination of naps for reducing performance decrements on the morning commute, whilst still preserving daytime sleep quality. Copyright © 2015 Elsevier Ltd. All rights reserved.

The C Terminus of the Histone Chaperone Asf1 Cross-Links to Histone H3 in Yeast and Promotes Interaction with Histones H3 and H4

PubMed Central

Dennehey, Briana K.; Noone, Seth; Liu, Wallace H.; Smith, Luke

2013-01-01

The central histone H3/H4 chaperone Asf1 comprises a highly conserved globular core and a divergent C-terminal tail. While the function and structure of the Asf1 core are well known, the function of the tail is less well understood. Here, we have explored the role of the yeast (yAsf1) and human (hAsf1a and hAsf1b) Asf1 tails in Saccharomyces cerevisiae. We show, using a photoreactive, unnatural amino acid, that Asf1 tail residue 210 cross-links to histone H3 in vivo and, further, that loss of C-terminal tail residues 211 to 279 weakens yAsf1-histone binding affinity in vitro nearly 200-fold. Via several yAsf1 C-terminal truncations and yeast-human chimeric proteins, we found that truncations at residue 210 increase transcriptional silencing and that the hAsf1a tail partially substitutes for full-length yAsf1 with respect to silencing but that full-length hAsf1b is a better overall substitute for full-length yAsf1. In addition, we show that the C-terminal tail of Asf1 is phosphorylated at T270 in yeast. Loss of this phosphorylation site does not prevent coimmunoprecipitation of yAsf1 and Rad53 from yeast extracts, whereas amino acid residue substitutions at the Asf1-histone H3/H4 interface do. Finally, we show that residue substitutions in yAsf1 near the CAF-1/HIRA interface also influence yAsf1's function in silencing. PMID:23184661

Associations between Longer Habitual Day Napping and Non-Alcoholic Fatty Liver Disease in an Elderly Chinese Population

PubMed Central

Qu, Hua; Wang, Hang; Deng, Min; Wei, Huili; Deng, Huacong

2014-01-01

Context Both longer habitual day napping and Non-Alcoholic Fatty Liver Disease (NAFLD) are associated with diabetes and inflammation, but the association between day napping and NAFLD remains unexplored. Objective To investigate the association between the duration of habitual day napping and NAFLD in an elderly Chinese population and to gain insight into the role of inflammatory cytokines in this association. Design and Setting We conducted a series of cross-sectional studies of the community population in Chongqing, China, from 2011 to 2012. Participants Among 6998 participants aged 40 to 75 years, 6438 eligible participants were included in the first study and analyzed to observe the association between day napping duration and NAFLD. In a separate study, 80 non-nappers and 90 nappers were selected to identify the role of inflammatory cytokines in this association. Logistic regression models were used to examine the odds ratios (ORs) of day nap duration with NAFLD. Results Day nappers had a significantly higher prevalence of NAFLD (P<0.001). Longer day napping duration was associated in a dose-dependent manner with NAFLD (P trend <0.001). After adjustment for potential confounders, the ORs were 1.67 (95% CI 1.13–2.46) for those reporting 0.5–1 h and 1.49 (95% CI 1.01–2.19) for those reporting >1 h of day napping compared with individuals who did not take day naps (all P<0.05). Longer-duration day nappers had higher levels of IL-6 and progranulin (PGRN) but lower levels of Secreted frizzled-related protein-5 (SFRP5, all P trend <0.001). After adjusting for IL-6, PGRN, and SFRP5, the association between day napping duration and NAFLD disappeared (all P>0.05). Conclusion Longer day napping duration is associated with a higher prevalence of NAFLD, and inflammatory cytokines may be an essential link between day napping and NAFLD. PMID:25140521

Napping Is Associated with Increased Risk of Type 2 Diabetes: The Guangzhou Biobank Cohort Study

PubMed Central

Lam, Kin-bong Hubert; Jiang, Chao Qiang; Thomas, G. Neil; Arora, Teresa; Zhang, Wei Sen; Taheri, Shahrad; Adab, Peymané; Lam, Tai Hing; Cheng, Kar Keung

2010-01-01

Study Objective: Intentional napping is very common, particularly in China. However, there are limited data regarding its potential health effects. We therefore examined the possible relationship between napping and type 2 diabetes. Design: Cross-sectional analysis of baseline data from the Guangzhou Biobank Cohort Study. Setting: Community-based elderly association in Guangzhou, China. Participants: 19,567 Chinese men and women aged 50 years or older. Measurements and Results: Self-reported frequency of napping was obtained by questionnaire and type 2 diabetes was assessed by fasting blood glucose and/or self-reports of physician diagnosis or treatment. Participants reporting frequent naps (4-6 days/week and daily) were 42% to 52% more likely to have diabetes. The relationships remained essentially unchanged after adjustments were made for demographics, lifestyle and sleep habits, health status, adiposity, and metabolic markers (odds ratio for diabetes 1.36 [95% CI 1.17–1.57] in 4-6 days/week, 1.28 [1.15–1.44] in daily nappers). Similar associations were found between napping and impaired fasting glucose. Removal of those with potential ill health and daytime sleepiness did not alter the observed associations. Conclusions: Napping is associated with elevated prevalence of diabetes and impaired fasting glucose in this older Chinese sample. Our finding suggests that it is less likely that diabetes leads to daytime sleepiness. This raises the possibility that napping may increase the risk of diabetes. Confirmation by longitudinal studies is needed. Citation: Lam KbH; Jiang CQ; Thomas GN; Arora T; Zhang WS; Taheri S; Adab P; Lam TH; Cheng KK. Napping is associated with increased risk of type 2 diabetes: the Guangzhou Biobank Cohort Study. SLEEP 2010;33(3):402-407. PMID:20337199

Zac1 is a histone acetylation-regulated NF-κB suppressor that mediates histone deacetylase inhibitor-induced apoptosis.

PubMed

Shu, G; Tang, Y; Zhou, Y; Wang, C; Song, J-G

2011-12-01

Histone deacetylase (HDAC) inhibitors are a class of promising anticancer reagents. They are able to induce apoptosis in embryonic carcinoma (EC) cells. However, the underlying mechanism remains poorly understood. Here we show that increased expression of zinc-finger protein regulator of apoptosis and cell-cycle arrest (Zac1) is implicated in HDAC inhibitor-induced apoptosis in F9 and P19 EC cells. By chromatin immunoprecipitation analysis we identified that increased Zac1 expression is mediated by histone acetylation of the Zac1 promoter region. Knockdown of Zac1 inhibited HDAC inhibitor-induced cell apoptosis. Moreover, HDAC inhibitors repressed nuclear factor-κB (NF-κB) activity, and this effect is abrogated by Zac1 knockdown. Consistently, Zac1 overexpression suppressed cellular NF-κB activity. Further investigation showed that Zac1 inhibits NF-κB activity by interacting with the C-terminus of the p65 subunit, which suppresses the phosphorylation of p65 at Ser468 and Ser536 residues. These results indicate that Zac1 is a histone acetylation-regulated suppressor of NF-κB, which is induced and implicated in HDAC inhibitor-mediated EC cell apoptosis.

Rootletin interacts with C-Nap1 and may function as a physical linker between the pair of centrioles/basal bodies in cells.

PubMed

Yang, Jun; Adamian, Michael; Li, Tiansen

2006-02-01

Rootletin, a major structural component of the ciliary rootlet, is located at the basal bodies and centrosomes in ciliated and nonciliated cells, respectively. Here we investigated its potential role in the linkage of basal bodies/centrioles and the mechanism involved in such linkages. We show that rootletin interacts with C-Nap1, a protein restricted at the ends of centrioles and functioning in centrosome cohesion in interphase cells. Their interaction in vivo is supported by their colocalization at the basal bodies/centrioles and coordinated association with the centrioles during the cell cycle. Ultrastructural examinations demonstrate that rootletin fibers connect the basal bodies in ciliated cells and are present both at the ends of and in between the pair of centrioles in nonciliated cells. The latter finding stands in contrast with C-Nap1, which is present only at the ends of the centrioles. Transient expression of C-Nap1 fragments dissociated rootletin fibers from the centrioles, resulting in centrosome separation in interphase. Overexpression of rootletin in cells caused multinucleation, micronucleation, and irregularity of nuclear shape and size, indicative of defects in chromosome separation. These data suggest that rootletin may function as a physical linker between the pair of basal bodies/centrioles by binding to C-Nap1.

A review of short naps and sleep inertia: do naps of 30 min or less really avoid sleep inertia and slow-wave sleep?

PubMed

Hilditch, Cassie J; Dorrian, Jillian; Banks, Siobhan

2017-04-01

Napping is a widely used countermeasure to sleepiness and impaired performance caused by sleep loss and circadian pressure. Sleep inertia, the period of grogginess and impaired performance experienced after waking, is a potential side effect of napping. Many industry publications recommend naps of 30 min or less to avoid this side effect. However, the evidence to support this advice is yet to be thoroughly reviewed. Electronic databases were searched, and defined criteria were applied to select articles for review. The review covers literature on naps of 30 min or less regarding (a) sleep inertia, (b) slow-wave sleep (SWS) and (c) the relationship between sleep inertia and SWS. The review found that although the literature on short afternoon naps is relatively comprehensive, there are very few studies on naps of 30 min or less at night. Studies have mixed results regarding the onset of SWS and the duration and severity of sleep inertia following short naps, making guidelines regarding their use unclear. The varying results are likely due to differing sleep/wake profiles before the nap of interest and the time of the day at waking. The review highlights the need to have more detailed guidelines about the implementation of short naps according to the time of the day and prior sleep/wake history. Without this context, such a recommendation is potentially misleading. Further research is required to better understand the interactions between these factors, especially at night, and to provide more specific recommendations. Copyright © 2017 Elsevier B.V. All rights reserved.

Preparative two-step purification of recombinant H1.0 linker histone and its domains.

PubMed

Ivic, Nives; Bilokapic, Silvija; Halic, Mario

2017-01-01

H1 linker histones are small basic proteins that have a key role in the formation and maintenance of higher-order chromatin structures. Additionally, many examples have shown that linker histones play an important role in gene regulation, modulated by their various subtypes and posttranslational modifications. Obtaining high amounts of very pure linker histones, especially for efficient antibody production, remains a demanding and challenging procedure. Here we present an easy and fast method to purify human linker histone H1.0 overexpressed in Escherichia coli, as well as its domains: N-terminal/globular domain and C-terminal intrinsically disordered domain. This purification protocol relies on a simple affinity chromatography step followed by cation exchange due to the highly basic properties of histone proteins. Therefore, this protocol can also be applied to other linker histones. Highly pure proteins in amounts sufficient for most biochemical experiments can be obtained. The functional quality of purified H1.0 histone and its domains has been confirmed by pull-down, gel-mobility shift assays and the nuclear import assay.

The functional interactome landscape of the human histone deacetylase family

PubMed Central

Joshi, Preeti; Greco, Todd M; Guise, Amanda J; Luo, Yang; Yu, Fang; Nesvizhskii, Alexey I; Cristea, Ileana M

2013-01-01

Histone deacetylases (HDACs) are a diverse family of essential transcriptional regulatory enzymes, that function through the spatial and temporal recruitment of protein complexes. As the composition and regulation of HDAC complexes are only partially characterized, we built the first global protein interaction network for all 11 human HDACs in T cells. Integrating fluorescence microscopy, immunoaffinity purifications, quantitative mass spectrometry, and bioinformatics, we identified over 200 unreported interactions for both well-characterized and lesser-studied HDACs, a subset of which were validated by orthogonal approaches. We establish HDAC11 as a member of the survival of motor neuron complex and pinpoint a functional role in mRNA splicing. We designed a complementary label-free and metabolic-labeling mass spectrometry-based proteomics strategy for profiling interaction stability among different HDAC classes, revealing that HDAC1 interactions within chromatin-remodeling complexes are largely stable, while transcription factors preferentially exist in rapid equilibrium. Overall, this study represents a valuable resource for investigating HDAC functions in health and disease, encompassing emerging themes of HDAC regulation in cell cycle and RNA processing and a deeper functional understanding of HDAC complex stability. PMID:23752268

Daytime napping, sleep duration and increased 8-year risk of type 2 diabetes in a British population.

PubMed

Leng, Y; Cappuccio, F P; Surtees, P G; Luben, R; Brayne, C; Khaw, K-T

2016-11-01

Few studies have prospectively examined the relationship between daytime napping and risk of type 2 diabetes. We aimed to study the effects of daytime napping and the joint effects of napping and sleep duration in predicting type 2 diabetes risk in a middle- to older-aged British population. In 1998-2000, 13 465 individuals with no known diabetes participating in the European Prospective Investigation into Cancer-Norfolk study reported daytime napping habit and 24-h sleep duration. Incident type 2 diabetes cases were identified through multiple data sources until 31 July 2006. After adjustment for age and sex, daytime napping was associated with a 58% higher diabetes risk. Further adjustment for education, marital status, smoking, alcohol intake, physical activity, comorbidities and hypnotic drug use had little influence on the association, but additional adjustment for BMI and Waist Circumference attenuated the Odds ratio (OR) (95% CI) to 1.30 (1.01, 1.69). The adjusted ORs (95% CI) associated with short and long sleep duration were 1.46 (1.10, 1.90) and 1.64 (1.16, 2.32), respectively. When sleep duration and daytime napping were examined together, the risk of developing diabetes more than doubled for those who took day naps and had less than 6 h of sleep, compared to those who did not nap and had 6-8 h of sleep. Daytime napping was associated with an increased risk of type 2 diabetes, particularly when combined with short sleep duration. Further physiological studies are needed to confirm the interaction between different domains of sleep in relation to diabetes risk. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Daytime Napping and the Risk of Cardiovascular Disease and All-Cause Mortality: A Prospective Study and Dose-Response Meta-Analysis.

PubMed

Yamada, Tomohide; Hara, Kazuo; Shojima, Nobuhiro; Yamauchi, Toshimasa; Kadowaki, Takashi

2015-12-01

To summarize evidence about the association between daytime napping and the risk of cardiovascular disease and all-cause mortality, and to quantify the potential dose-response relation. Meta-analysis of prospective cohort studies. Electronic databases were searched for articles published up to December 2014 using the terms nap, cardiovascular disease, and all-cause mortality. We selected well-adjusted prospective cohort studies reporting risk estimates for cardiovascular disease and all-cause mortality related to napping. Eleven prospective cohort studies were identified with 151,588 participants (1,625,012 person-years) and a mean follow-up period of 11 years (60% women, 5,276 cardiovascular events, and 18,966 all-cause deaths). Pooled analysis showed that a long daytime nap (≥ 60 min/day) was associated with a higher risk of cardiovascular disease (rate ratio [RR]: 1.82 [1.22-2.71], P = 0.003, I(2) = 37%) compared with not napping. All-cause mortality was associated with napping for ≥ 60 min/day (RR: 1.27 [1.11-1.45], P < 0.001, I(2) = 0%) compared with not napping. In contrast, napping for < 60 min/day was not associated with cardiovascular disease (P = 0.98) or all-cause mortality (P = 0.08). Meta-analysis demonstrated a significant J-curve dose-response relation between nap time and cardiovascular disease (P for nonlinearity = 0.01). The RR initially decreased from 0 to 30 min/day. Then it increased slightly until about 45 min/day, followed by a sharp increase at longer nap times. There was also a positive linear relation between nap time and all-cause mortality (P for non-linearity = 0.97). Nap time and cardiovascular disease may be associated via a J-curve relation. Further studies are needed to confirm the efficacy of a short nap. © 2015 Associated Professional Sleep Societies, LLC.

Interactions of Histone Acetyltransferase p300 with the Nuclear Proteins Histone and HMGB1, As Revealed by Single Molecule Atomic Force Spectroscopy.

PubMed

Banerjee, S; Rakshit, T; Sett, S; Mukhopadhyay, R

2015-10-22

One of the important properties of the transcriptional coactivator p300 is histone acetyltransferase (HAT) activity that enables p300 to influence chromatin action via histone modulation. p300 can exert its HAT action upon the other nuclear proteins too--one notable example being the transcription-factor-like protein HMGB1, which functions also as a cytokine, and whose accumulation in the cytoplasm, as a response to tissue damage, is triggered by its acetylation. Hitherto, no information on the structure and stability of the complexes between full-length p300 (p300FL) (300 kDa) and the histone/HMGB1 proteins are available, probably due to the presence of unstructured regions within p300FL that makes it difficult to be crystallized. Herein, we have adopted the high-resolution atomic force microscopy (AFM) approach, which allows molecularly resolved three-dimensional contour mapping of a protein molecule of any size and structure. From the off-rate and activation barrier values, obtained using single molecule dynamic force spectroscopy, the biochemical proposition of preferential binding of p300FL to histone H3, compared to the octameric histone, can be validated. Importantly, from the energy landscape of the dissociation events, a model for the p300-histone and the p300-HMGB1 dynamic complexes that HAT forms, can be proposed. The lower unbinding forces of the complexes observed in acetylating conditions, compared to those observed in non-acetylating conditions, indicate that upon acetylation, p300 tends to weakly associate, probably as an outcome of charge alterations on the histone/HMGB1 surface and/or acetylation-induced conformational changes. To our knowledge, for the first time, a single molecule level treatment of the interactions of HAT, where the full-length protein is considered, is being reported.

Microtubules (tau) as an emerging therapeutic target: NAP (davunetide).

PubMed

Gozes, Illana

2011-01-01

This review focuses on the discovery of activity-dependent neuroprotective protein (ADNP) and the ensuing discovery of NAP (davunetide) toward clinical development with emphasis on microtubule protection. ADNP immunoreactivity was shown to occasionally decorate microtubules and ADNP silencing inhibited neurite outgrowth as measured by microtubule associated protein 2 (MAP2) labeling. ADNP knockout is lethal, while 50% reduction in ADNP (ADNP haploinsufficiency) resulted in the microtubule associated protein tau pathology coupled to cognitive dysfunction and neurodegeneration. NAP (davunetide), an eight amino acid peptide derived from ADNP partly ameliorated deficits associated with ADNP deficiency. NAP (davunetide) interacted with microtubules, protected against microtubule toxicity associated with zinc, nocodazole and oxidative stress in vitro and against tau pathology and MAP6 (stable tubuleonly polypeptide - STOP) pathology in vivo. NAP (davunetide) provided neurotrophic functions promoting neurite outgrowth as measured by increases in MAP2 immunoreactivity and synapse formation by increasing synaptophysin expression. NAP (davunetide) protection against neurodegeneration has recently been shown to extend to katanin-related microtubule disruption under conditions of tau deficiencies. In conclusion, NAP (davunetide) provided potent neuroprotection in a broad range of neurodegenerative models, protecting the neuroglial cytoskeleton in vitro and inhibiting tau pathology (tauopathy) in vivo. Based on these extensive preclinical results, davunetide (NAP) is now being evaluated in a Phase II/III study of the tauopathy, progressive supranuclear palsy (PSP); (Allon Therapeutics Inc.).

Sleep inertia associated with a 10-min nap before the commute home following a night shift: A laboratory simulation study.

PubMed

Hilditch, Cassie J; Dorrian, Jillian; Centofanti, Stephanie A; Van Dongen, Hans P; Banks, Siobhan

2017-02-01

Night shift workers are at risk of road accidents due to sleepiness on the commute home. A brief nap at the end of the night shift, before the commute, may serve as a sleepiness countermeasure. However, there is potential for sleep inertia, i.e. transient impairment immediately after awakening from the nap. We investigated whether sleep inertia diminishes the effectiveness of napping as a sleepiness countermeasure before a simulated commute after a simulated night shift. N=21 healthy subjects (aged 21-35 y; 12 females) participated in a 3-day laboratory study. After a baseline night, subjects were kept awake for 27h for a simulated night shift. They were randomised to either receive a 10-min nap ending at 04:00 plus a 10-min pre-drive nap ending at 07:10 (10-NAP) or total sleep deprivation (NO-NAP). A 40-min York highway driving task was performed at 07:15 to simulate the commute. A 3-min psychomotor vigilance test (PVT-B) and the Samn-Perelli Fatigue Scale (SP-Fatigue) were administered at 06:30 (pre-nap), 07:12 (post-nap), and 07:55 (post-drive). In the 10-NAP condition, total pre-drive nap sleep time was 9.1±1.2min (mean±SD), with 1.3±1.9min spent in slow wave sleep, as determined polysomnographically. There was no difference between conditions in PVT-B performance at 06:30 (before the nap). In the 10-NAP condition, PVT-B performance was worse after the nap (07:12) compared to before the nap (06:30); no change across time was found in the NO-NAP condition. There was no significant difference between conditions in PVT-B performance after the drive. SP-Fatigue and driving performance did not differ significantly between conditions. In conclusion, the pre-drive nap showed objective, but not subjective, evidence of sleep inertia immediately after awakening. The 10-min nap did not affect driving performance during the simulated commute home, and was not effective as a sleepiness countermeasure. Copyright © 2015 Elsevier Ltd. All rights reserved.

Histone chaperones: assisting histone traffic and nucleosome dynamics.

PubMed

Gurard-Levin, Zachary A; Quivy, Jean-Pierre; Almouzni, Geneviève

2014-01-01

The functional organization of eukaryotic DNA into chromatin uses histones as components of its building block, the nucleosome. Histone chaperones, which are proteins that escort histones throughout their cellular life, are key actors in all facets of histone metabolism; they regulate the supply and dynamics of histones at chromatin for its assembly and disassembly. Histone chaperones can also participate in the distribution of histone variants, thereby defining distinct chromatin landscapes of importance for genome function, stability, and cell identity. Here, we discuss our current knowledge of the known histone chaperones and their histone partners, focusing on histone H3 and its variants. We then place them into an escort network that distributes these histones in various deposition pathways. Through their distinct interfaces, we show how they affect dynamics during DNA replication, DNA damage, and transcription, and how they maintain genome integrity. Finally, we discuss the importance of histone chaperones during development and describe how misregulation of the histone flow can link to disease.

Post-translational modifications of linker histone H1 variants in mammals

NASA Astrophysics Data System (ADS)

Starkova, T. Yu; Polyanichko, A. M.; Artamonova, T. O.; Khodorkovskii, M. A.; Kostyleva, E. I.; Chikhirzhina, E. V.; Tomilin, A. N.

2017-02-01

The covalent modifications of the linker histone H1 and the core histones are thought to play an important role in the control of chromatin functioning. Histone H1 variants from K562 cell line (hH1), mouse (mH1) and calf (cH1) thymi were studied by matrix-activated laser desorption/ionization fourier transform ion cyclotron resonance mass-spectroscopy (MALDI-FT-ICR-MS). The proteomics analysis revealed novel post-translational modifications of the histone H1, such as meK34-mH1.4, meK35-cH1.1, meK35-mH1.1, meK75-hH1.2, meK75-hH1.3, acK26-hH1.4, acK26-hH1.3 and acK17-hH1.1. The comparison of the hH1, mH1 and cH1 proteins has demonstrated that the types and positions of the post-translational modifications of the globular domains of the H1.2-H1.4 variants are very conservative. However, the post-translational modifications of the N- and C-terminal tails of H1.2, H1.3 and H1.4 are different. The differences of post-translational modifications in the N- and C-terminal tails of H1.2, H1.3 and H1.4 likely lead to the differences in DNA-H1 and H1-protein interactions.

Affinity Map of Bromodomain Protein 4 (BRD4) Interactions with the Histone H4 Tail and the Small Molecule Inhibitor JQ1*

PubMed Central

Jung, Marie; Philpott, Martin; Müller, Susanne; Schulze, Jessica; Badock, Volker; Eberspächer, Uwe; Moosmayer, Dieter; Bader, Benjamin; Schmees, Norbert; Fernández-Montalván, Amaury; Haendler, Bernard

2014-01-01

Bromodomain protein 4 (BRD4) is a member of the bromodomain and extra-terminal domain (BET) protein family. It binds to acetylated histone tails via its tandem bromodomains BD1 and BD2 and forms a complex with the positive transcription elongation factor b, which controls phosphorylation of RNA polymerase II, ultimately leading to stimulation of transcription elongation. An essential role of BRD4 in cell proliferation and cancer growth has been reported in several recent studies. We analyzed the binding of BRD4 BD1 and BD2 to different partners and showed that the strongest interactions took place with di- and tetra-acetylated peptides derived from the histone 4 N-terminal tail. We also found that several histone 4 residues neighboring the acetylated lysines significantly influenced binding. We generated 10 different BRD4 BD1 mutants and analyzed their affinities to acetylated histone tails and to the BET inhibitor JQ1 using several complementary biochemical and biophysical methods. The impact of these mutations was confirmed in a cellular environment. Altogether, the results show that Trp-81, Tyr-97, Asn-140, and Met-149 play similarly important roles in the recognition of acetylated histones and JQ1. Pro-82, Leu-94, Asp-145, and Ile-146 have a more differentiated role, suggesting that different kinds of interactions take place and that resistance mutations compatible with BRD4 function are possible. Our study extends the knowledge on the contribution of individual BRD4 amino acids to histone and JQ1 binding and may help in the design of new BET antagonists with improved pharmacological properties. PMID:24497639

Regulation of androgen receptor and histone deacetylase 1 by Mdm2-mediated ubiquitylation.

PubMed

Gaughan, Luke; Logan, Ian R; Neal, David E; Robson, Craig N

2005-01-01

The androgen receptor (AR) is a member of the nuclear hormone receptor family of transcription factors and plays a critical role in regulating the expression of genes involved in androgen-dependent and -independent tumour formation. Regulation of the AR is achieved by alternate binding of either histone acetyltransferase (HAT)-containing co-activator proteins, or histone deacetylase 1 (HDAC1). Factors that control AR stability may also constitute an important regulatory mechanism, a notion that has been confirmed with the finding that the AR is a direct target for Mdm2-mediated ubiquitylation and proteolysis. Using chromatin immunoprecipitation (ChIP) and re-ChIP analyses, we show that Mdm2 associates with AR and HDAC1 at the active androgen-responsive PSA promoter in LNCaP prostate cancer cells. Furthermore, we demonstrate that Mdm2-mediated modification of AR and HDAC1 catalyses protein destabilization and attenuates AR sactivity, suggesting that ubiquitylation of the AR and HDAC1 may constitute an additional mechanism for regulating AR function. We also show that HDAC1 and Mdm2 function co-operatively to reduce AR-mediated transcription that is attenuated by the HAT activity of the AR co-activator Tip60, suggesting interplay between acetylation status and receptor ubiquitylation in AR regulation. In all, our data indicates a novel role for Mdm2 in regulating components of the AR transcriptosome.

Effects of afternoon "siesta" naps on sleep, alertness, performance, and circadian rhythms in the elderly

NASA Technical Reports Server (NTRS)

Monk, T. H.; Buysse, D. J.; Carrier, J.; Billy, B. D.; Rose, L. R.

2001-01-01

STUDY OBJECTIVES: To determine the effects of a 90-minute afternoon nap regimen on nocturnal sleep, circadian rhythms, and evening alertness and performance levels in the healthy elderly. DESIGN AND SETTING: Nine healthy elderly subjects (4m, 5f, age range 74y-87y) each experienced both nap and no-nap conditions in two studies each lasting 17 days (14 at home, 3 in the laboratory). In the nap condition a 90-minute nap was enforced between 13:30 and 15:00 every day, in the no-nap condition daytime napping was prohibited, and activity encouraged in the 13:30-15:00 interval. The order of the two conditions was counterbalanced. PARTICIPANTS: N/A INTERVENTIONS: N/A MEASUREMENTS: Diary measures, pencil and paper alertness tests, and wrist actigraphy were used at home. In the 72 hour laboratory studies, these measures were augmented by polysomnographic sleep recording, continuous rectal temperature measurement, a daily evening single trial of a Multiple Sleep Latency Test (MSLT), and computerized tests of mood, activation and performance efficiency. RESULTS: By the second week in the "at home" study, an average of 58 minutes of sleep was reported per siesta nap; in the laboratory, polysomnography confirmed an average of 57 minutes of sleep per nap. When nap and no-nap conditions were compared, mixed effects on nocturnal sleep were observed. Diary measures indicated no significant difference in nocturnal sleep duration, but a significant increase (of 38 mins.) in 24-hour Total Sleep Time (TST) when nocturnal sleeps and naps were added together (p<0.025). The laboratory study revealed a decrease of 2.4% in nocturnal sleep efficiency in the nap condition (p<0.025), a reduction of nocturnal Total Sleep Time (TST) by 48 mins. in the nap condition (p<0.001) which resulted primarily from significantly earlier waketimes (p<0.005), but no reliable effects on Wake After Sleep Onset (WASO), delta sleep measures, or percent stages 1 & 2. Unlike the diary study, the laboratory study

Napping reverses increased pain sensitivity due to sleep restriction.

PubMed

Faraut, Brice; Léger, Damien; Medkour, Terkia; Dubois, Alexandre; Bayon, Virginie; Chennaoui, Mounir; Perrot, Serge

2015-01-01

To investigate pain sensitivity after sleep restriction and the restorative effect of napping. A strictly controlled randomized crossover study with continuous polysomnography monitoring was performed. Laboratory-based study. 11 healthy male volunteers. Volunteers attended two three-day sessions: "sleep restriction" alone and "sleep restriction and nap". Each session involved a baseline night of normal sleep, a night of sleep deprivation and a night of free recovery sleep. Participants were allowed to sleep only from 02:00 to 04:00 during the sleep deprivation night. During the "sleep restriction and nap" session, volunteers took two 30-minute naps, one in the morning and one in the afternoon. Quantitative sensory testing was performed with heat, cold and pressure, at 10:00 and 16:00, on three areas: the supraspinatus, lower back and thigh. After sleep restriction, quantitative sensory testing revealed differential changes in pain stimuli thresholds, but not in thermal threshold detection: lower back heat pain threshold decreased, pressure pain threshold increased in the supraspinatus area and no change was observed for the thigh. Napping restored responses to heat pain stimuli in the lower back and to pressure stimuli in the supraspinatus area. Sleep restriction induces different types of hypersensitivity to pain stimuli in different body areas, consistent with multilevel mechanisms, these changes being reversed by napping. The napping restorative effect on pain thresholds result principally from effects on pain mechanisms, since it was independent of vigilance status.

The utility of a 5(th) nap in multiple sleep latency test.

PubMed

Muza, Rexford; Lykouras, Dimosthenis; Rees, Kate

2016-02-01

This is the first study that aimed to look specifically at the utility of the 5(th) nap in the multiple sleep latency test (MSLT), a test used to assist in the diagnosis of narcolepsy. Data was retrospectively collected from the Sleep Disorders Centre of a Tertiary Hospital on patients that had a 5(th) nap during their MSLT from the 08(th) November 2011 to 12(th) November 2014. Fifty-three patients had a 5(th) nap performed out of 378 MSLT studies. In 16% of cases a diagnosis of narcolepsy was given directly due to the inclusion of the 5(th) nap on the MSLT. Here a 5(th) nap allowed diagnostic criteria of mean sleep latency <8 minutes and >2 SOREMPS to be met. In 53% of cases the mean sleep latency increased due to 5(th) nap inclusion; the mean sleep latency of the first four naps was 5.6 vs. 6.7 after inclusion of the 5(th) nap. The 5(th) nap is not often performed within the MSLT studies. Our study shows that only a few patients may benefit from a 5(th) nap opportunity which also led to increase of the mean sleep latency at the expense of extra time, cost, labour and increased patient anxiety.

Scheduled napping as a countermeasure to sleepiness in air traffic controllers.

PubMed

Signal, Tracey Leigh; Gander, Philippa H; Anderson, Howard; Brash, Sue

2009-03-01

The aims of this study were to measure sleep during a planned nap on the night shift; and to use objective measures of performance and alertness to compare the effects of the nap opportunity versus staying awake. Twenty-eight air traffic controllers (mean age 36 years, nine women) completed four night shifts (two with early starts and two with late starts). Each type of night shift (early/late start) included a 40-min planned nap opportunity on one occasion and no nap on the other. Polysomnographic data were used to measure sleep and waking alertness [spectral power in the electroencephalogram (EEG) during the last hour of the night shift and the occurrence of slow rolling eye movements (SEMs) subsequent to the nap]. Psychomotor performance task [Psychomotor Vigilance Task (PVT)] was completed at the beginning and end of the shift, and after the nap (or an equivalent time if no nap was taken). Nap sleep latencies were relatively long (mean = 19 min) and total sleep time short (mean = 18 min), with minimal slow wave sleep (SWS, mean = 0%), and no rapid eye movement sleep. Nap sleep resulted in improved PVT performance (mean and slowest 10% of reaction time events), decreased spectral power in the EEG and reduced the likelihood of SEMs. The occurrence of SWS in the nap decreased spectral power in the EEG. This study indicates that although sleep taken at work is likely to be short and of poor quality it still results in an improvement in objective measures of alertness and performance.

Afternoon nap and bright light exposure improve cognitive flexibility post lunch.

PubMed

Slama, Hichem; Deliens, Gaétane; Schmitz, Rémy; Peigneux, Philippe; Leproult, Rachel

2015-01-01

Beneficial effects of napping or bright light exposure on cognitive performance have been reported in participants exposed to sleep loss. Nonetheless, few studies investigated the effect of these potential countermeasures against the temporary drop in performance observed in mid-afternoon, and even less so on cognitive flexibility, a crucial component of executive functions. This study investigated the impact of either an afternoon nap or bright light exposure on post-prandial alterations in task switching performance in well-rested participants. Twenty-five healthy adults participated in two randomized experimental conditions, either wake versus nap (n=15), or bright light versus placebo (n=10). Participants were tested on a switching task three times (morning, post-lunch and late afternoon sessions). The interventions occurred prior to the post-lunch session. In the nap/wake condition, participants either stayed awake watching a 30-minute documentary or had the opportunity to take a nap for 30 minutes. In the bright light/placebo condition, participants watched a documentary under either bright blue light or dim orange light (placebo) for 30 minutes. The switch cost estimates cognitive flexibility and measures task-switching efficiency. Increased switch cost scores indicate higher difficulties to switch between tasks. In both control conditions (wake or placebo), accuracy switch-cost score increased post lunch. Both interventions (nap or bright light) elicited a decrease in accuracy switch-cost score post lunch, which was associated with diminished fatigue and decreased variability in vigilance. Additionally, there was a trend for a post-lunch benefit of bright light with a decreased latency switch-cost score. In the nap group, improvements in accuracy switch-cost score were associated with more NREM sleep stage N1. Thus, exposure to bright light during the post-lunch dip, a countermeasure easily applicable in daily life, results in similar beneficial effects as

Afternoon Nap and Bright Light Exposure Improve Cognitive Flexibility Post Lunch

PubMed Central

Schmitz, Rémy; Peigneux, Philippe; Leproult, Rachel

2015-01-01

Beneficial effects of napping or bright light exposure on cognitive performance have been reported in participants exposed to sleep loss. Nonetheless, few studies investigated the effect of these potential countermeasures against the temporary drop in performance observed in mid-afternoon, and even less so on cognitive flexibility, a crucial component of executive functions. This study investigated the impact of either an afternoon nap or bright light exposure on post-prandial alterations in task switching performance in well-rested participants. Twenty-five healthy adults participated in two randomized experimental conditions, either wake versus nap (n=15), or bright light versus placebo (n=10). Participants were tested on a switching task three times (morning, post-lunch and late afternoon sessions). The interventions occurred prior to the post-lunch session. In the nap/wake condition, participants either stayed awake watching a 30-minute documentary or had the opportunity to take a nap for 30 minutes. In the bright light/placebo condition, participants watched a documentary under either bright blue light or dim orange light (placebo) for 30 minutes. The switch cost estimates cognitive flexibility and measures task-switching efficiency. Increased switch cost scores indicate higher difficulties to switch between tasks. In both control conditions (wake or placebo), accuracy switch-cost score increased post lunch. Both interventions (nap or bright light) elicited a decrease in accuracy switch-cost score post lunch, which was associated with diminished fatigue and decreased variability in vigilance. Additionally, there was a trend for a post-lunch benefit of bright light with a decreased latency switch-cost score. In the nap group, improvements in accuracy switch-cost score were associated with more NREM sleep stage N1. Thus, exposure to bright light during the post-lunch dip, a countermeasure easily applicable in daily life, results in similar beneficial effects as

Short Daytime Naps Briefly Attenuate Objectively Measured Sleepiness Under Chronic Sleep Restriction.

PubMed

Saletin, Jared M; Hilditch, Cassie J; Dement, William C; Carskadon, Mary A

2017-09-01

Napping is a useful countermeasure to the negative effects of acute sleep loss on alertness. The efficacy of naps to recover from chronic sleep loss is less well understood. Following 2 baseline nights (10 hours' time-in-bed), participants were restricted to 7 nights of 5-hour sleep opportunity. Ten adults participated in the No-Nap condition, and a further 9 were assigned to a Nap condition with a daily 45-minute nap opportunity at 1300 h. Sleepiness was assessed using the multiple sleep latency test and a visual analogue scale at 2-hour intervals. Both objective and subjective indexes of sleepiness were normalized within subject as a difference from those at baseline prior to sleep restriction. Mixed-effects models examined how the daytime nap opportunity altered sleepiness across the day and across the protocol. Short daytime naps attenuated sleepiness due to chronic sleep restriction for up to 6-8 hours after the nap. Benefits of the nap did not extend late into evening. Subjective sleepiness demonstrated a similar short-lived benefit that emerged later in the day when objective sleepiness already returned to pre-nap levels. Neither measure showed a benefit of the nap the following morning after the subsequent restriction night. These data indicate a short daytime nap may attenuate sleepiness in chronic sleep restriction, yet subjective and objective benefits emerge at different time scales. Because neither measure showed a benefit the next day, the current study underscores the need for careful consideration before naps are used as routine countermeasures to chronic sleep loss. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

The Relationship Between Midday Napping And Neurocognitive Function in Early Adolescents.

PubMed

Ji, Xiaopeng; Li, Junxin; Liu, Jianghong

2018-02-01

The impact of midday napping on neurocognitive function in adolescents has not been well established. This study aimed to investigate the relationship between self-reported midday-napping behaviors and neurocognitive function in early adolescents. The sample was comprised of 363 early adolescents (12.00 ± 0.38 years old) from Jintan, China. Midday napping, nighttime sleep duration, and sleep quality were measured by self-reported questionnaires. Neurocognitive function was measured by the Penn Computerized Neurocognitive Battery (accuracy and reaction times). Generalized linear regression was used to analyze the relationships. Sixty-four percent of our sample took more than 3 naps per week, and 70.11% reported nap durations of over 30 min. Participants with higher frequencies or longer durations of midday napping reported significantly better nighttime sleep quality (p < 0.05). Adjusted models showed that frequent nappers (5-7d/week) were significantly associated with heightened accuracy on tasks that measured sustained attention and nonverbal reasoning and faster reaction times on spatial memory compared with other frequency groups (ps < 0.05). For napping duration subgroups, early adolescents who took naps of any length were estimated to have faster reaction speeds on the sustained attention task compared with participants who never napped (ps < 0.05). However, only nappers with a moderate duration (31-60 min) tended to achieve both faster speeds (β = -38.28, p = 0.02) and better accuracy (β = 3.90, p = 0.04) on the sustained attention task. Our findings suggest that there is an association between habitual midday napping and neurocognitive function in early adolescents, especially in China, where midday napping is a cultural practice.

Modification of Tet1 and histone methylation dynamics in dairy goat male germline stem cells.

PubMed

Zheng, Liming; Zhai, Yuanxin; Li, Na; Wu, Chongyang; Zhu, Haijing; Wei, Zhuying; Bai, Chunling; Li, Guangpeng; Hua, Jinlian

2016-04-01

Tet (ten-eleven translocation) protein 1 is a key enzyme for DNA demethylation, which modulates DNA methylation and gene transcription. DNA methylation and histone methylation are critical elements in self-renewal of male germline stem cells (mGSCs) and spermatogenesis. mGSCs are the only type of adult stem cells able to achieve intergenerational transfer of genetic information, which is accomplished through differentiated sperm cells. However, numerous epigenetic obstacles including incomplete DNA methylation and histone methylation dynamics make establishment of stable livestock mGSC cell lines difficult. The present study was conducted to detect effects of DNA methylation and histone methylation dynamics in dairy goat mGSCs self-renewal and proliferation, through overexpression of Tet1. An immortalized dairy goat mGSC cell line bearing mouse Tet1 (mTet1) gene was screened and characteristics of the cells were assayed by quantitative real-time PCR (qRT-PCR), immunofluorescence assay, western blotting, fluorescence activated cell sorting (FACS) and use of the cell counting kit (CCK8) assay. The screened immortalized dairy goat mGSC cell line bearing mTet1, called mGSC-mTet1 cells was treated with optimal doxycycline (Dox) concentration to maintain Tet1 gene expression. mGSC-mTet1 cells proliferated at a significantly greater rate than wild-type mGSCs, and mGSCs-specific markers such as proliferating cell nuclear antigen (PCNA), cyclinD1 (CCND1), GDNF family receptor alpha 1 (Gfra1) and endogenic Tet1, Tet2 were upregulated. The cells exhibited not only reduction in level of histone methylation but also changes in nuclear location of that methylation marker. While H3K9me3 was uniformly distributed throughout the nucleus of mGSC-mTet1 cells, it was present in only particular locations in mGSCs. H3K27me3 was distributed surrounding the edges of nuclei of mGSC-mTet1 cells, while it was uniformly distributed throughout nuclei of mGSCs. Our results conclusively

Esperanto for histones: CENP-A, not CenH3, is the centromeric histone H3 variant.

PubMed

Earnshaw, W C; Allshire, R C; Black, B E; Bloom, K; Brinkley, B R; Brown, W; Cheeseman, I M; Choo, K H A; Copenhaver, G P; Deluca, J G; Desai, A; Diekmann, S; Erhardt, S; Fitzgerald-Hayes, M; Foltz, D; Fukagawa, T; Gassmann, R; Gerlich, D W; Glover, D M; Gorbsky, G J; Harrison, S C; Heun, P; Hirota, T; Jansen, L E T; Karpen, G; Kops, G J P L; Lampson, M A; Lens, S M; Losada, A; Luger, K; Maiato, H; Maddox, P S; Margolis, R L; Masumoto, H; McAinsh, A D; Mellone, B G; Meraldi, P; Musacchio, A; Oegema, K; O'Neill, R J; Salmon, E D; Scott, K C; Straight, A F; Stukenberg, P T; Sullivan, B A; Sullivan, K F; Sunkel, C E; Swedlow, J R; Walczak, C E; Warburton, P E; Westermann, S; Willard, H F; Wordeman, L; Yanagida, M; Yen, T J; Yoda, K; Cleveland, D W

2013-04-01

The first centromeric protein identified in any species was CENP-A, a divergent member of the histone H3 family that was recognised by autoantibodies from patients with scleroderma-spectrum disease. It has recently been suggested to rename this protein CenH3. Here, we argue that the original name should be maintained both because it is the basis of a long established nomenclature for centromere proteins and because it avoids confusion due to the presence of canonical histone H3 at centromeres.

No first night shift effect observed following a nocturnal main sleep and a prophylactic 1-h afternoon nap.

PubMed

Kosmadopoulos, Anastasi; Zhou, Xuan; Roach, Gregory D; Darwent, David; Sargent, Charli

Neurobehavioural impairment on the first night shift is often greater than on subsequent night shifts due to extended wakefulness. The aim of the study was to determine whether a 1-h afternoon nap prior to the first night shift is sufficient to produce neurobehavioural performance at levels comparable to the second night shift. Twelve male volunteers (mean age 22.9 years) participated in a laboratory protocol that simulated two 12-h night shifts. A nap preceded the first shift and a 7-h daytime sleep was scheduled between shifts. Neurobehavioural performance and subjective sleepiness measured across each night did not significantly differ between first and second shifts.

High levels of histones promote whole-genome-duplications and trigger a Swe1WEE1-dependent phosphorylation of Cdc28CDK1

PubMed Central

Peñate, Xenia; Sanmartín Olmo, Trinidad; Jourquin, Frederic; Muñoz Centeno, Maria Cruz; Mendoza, Manuel; Simon, Marie-Noelle; Chavez, Sebastian

2018-01-01

Whole-genome duplications (WGDs) have played a central role in the evolution of genomes and constitute an important source of genome instability in cancer. Here, we show in Saccharomyces cerevisiae that abnormal accumulations of histones are sufficient to induce WGDs. Our results link these WGDs to a reduced incorporation of the histone variant H2A.Z to chromatin. Moreover, we show that high levels of histones promote Swe1WEE1 stabilisation thereby triggering the phosphorylation and inhibition of Cdc28CDK1 through a mechanism different of the canonical DNA damage response. Our results link high levels of histones to a specific type of genome instability that is quite frequently observed in cancer and uncovers a new mechanism that might be able to respond to high levels of histones. PMID:29580382

Short sleep duration and longer daytime napping are associated with non-alcoholic fatty liver disease in Chinese adults.

PubMed

Peng, Kui; Lin, Lin; Wang, Zhengyi; Ding, Lin; Huang, Ya; Wang, Po; Xu, Yu; Lu, Jieli; Xu, Min; Bi, Yufang; Wang, Weiqing; Chen, Yuhong; Ning, Guang

2017-09-01

Epidemiologic studies have reported conflicting results on the relationship between short sleep duration and non-alcoholic fatty liver disease (NAFLD). There are no previous studies investigating the effect of daytime napping on NAFLD. In the present study we examined the associations between NAFLD and both nightly sleep duration and daytime napping in a middle-aged and elderly Chinese population. This cross-sectional community-based population study was performed on 8559 individuals aged ≥40 years. Sleep duration and the duration of daytime napping were self-reported using a standardized questionnaire; NAFLD was diagnosed by ultrasonography. In this study sample, the overall prevalence of NAFLD was 30.4%. There was an inverse association between sleep duration and the risk of prevalent NAFLD. In multivariate analysis, the odds ratios (ORs) and 95% confidence intervals (CIs) of prevalent NAFLD for decreasing sleep duration categories (≥9, 8.1-9, 7.1-8, 6.1-7, and ≤6.1 h) were 1.00 (reference), 1.38 (1.13-1.70), 1.32 (1.08-1.61), 1.29 (1.04-1.60), and 1.66 (1.28-2.15), respectively (P trend  = 0.0073). Compared with participants without a daytime napping habit, nap takers with a longer nap duration (>0.5 h) had an increased risk of prevalent NAFLD (OR 1.22; 95% CI 1.06-1.41). The associations of sleep duration and daytime napping duration with NAFLD were generally consistent across different categories of age and obesity, metabolic syndrome, and insulin resistance status. Short sleep duration and longer daytime napping were associated with an increased risk of prevalent NAFLD in a middle-aged and elderly Chinese population. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Racial Differences in Reported Napping and Nocturnal Sleep in 2- to 8-Year-Old Children

PubMed Central

Crosby, Brian; LeBourgeois, Monique K.; Harsh, John

2010-01-01

Objectives The objectives of this study were to examine racial differences in reported napping and nighttime sleep of 2- to 8-year-old children, to identify factors accounting for these differences, and to determine if variability in napping was related to psychosocial functioning. Methods Caretakers of 1043 children (73.5% non-Hispanic white; 50.4% male) 2 to 8 years old from a community sample reported on their children’s napping behavior and nighttime sleep. Caretakers of 255 preschool children (3–5 years old) also completed the Behavior Assessment System for Children. Results A more gradual age-related decline in napping was found for black children. At age 8, 39.1% of black children were reported to nap, compared with only 4.9% of white children. Black children also napped significantly more days per week, had shorter average nocturnal sleep durations, and slept significantly less on weekdays than on weekend nights. Despite differences in sleep distribution, total weekly sleep duration (diurnal and nocturnal) was nearly identical for the 2 racial groups at each year of age. Logistic regression analysis revealed that demographic variables were related to but did not fully explain napping differences. Napping in a subset of preschoolers was not significantly related to psychosocial functioning. Conclusions There are remarkable racial differences in reported napping and nighttime sleep patterns beginning as early as age 3 and extending to at least 8 years of age. These differences are independent of commonly investigated demographic factors. Differences in napping behavior do not seem to have psychosocial significance in a sample of preschool children. PMID:15866856

Daytime Napping and the Risk of Cardiovascular Disease and All-Cause Mortality: A Prospective Study and Dose-Response Meta-Analysis

PubMed Central

Yamada, Tomohide; Hara, Kazuo; Shojima, Nobuhiro; Yamauchi, Toshimasa; Kadowaki, Takashi

2015-01-01

Study Objectives: To summarize evidence about the association between daytime napping and the risk of cardiovascular disease and all-cause mortality, and to quantify the potential dose-response relation. Design: Meta-analysis of prospective cohort studies. Methods and Results: Electronic databases were searched for articles published up to December 2014 using the terms nap, cardiovascular disease, and all-cause mortality. We selected well-adjusted prospective cohort studies reporting risk estimates for cardiovascular disease and all-cause mortality related to napping. Eleven prospective cohort studies were identified with 151,588 participants (1,625,012 person-years) and a mean follow-up period of 11 years (60% women, 5,276 cardiovascular events, and 18,966 all-cause deaths). Pooled analysis showed that a long daytime nap (≥ 60 min/day) was associated with a higher risk of cardiovascular disease (rate ratio [RR]: 1.82 [1.22–2.71], P = 0.003, I2 = 37%) compared with not napping. All-cause mortality was associated with napping for ≥ 60 min/day (RR: 1.27 [1.11–1.45], P < 0.001, I2 = 0%) compared with not napping. In contrast, napping for < 60 min/day was not associated with cardiovascular disease (P = 0.98) or all-cause mortality (P = 0.08). Meta-analysis demonstrated a significant J-curve dose-response relation between nap time and cardiovascular disease (P for nonlinearity = 0.01). The RR initially decreased from 0 to 30 min/day. Then it increased slightly until about 45 min/day, followed by a sharp increase at longer nap times. There was also a positive linear relation between nap time and all-cause mortality (P for non-linearity = 0.97). Conclusions: Nap time and cardiovascular disease may be associated via a J-curve relation. Further studies are needed to confirm the efficacy of a short nap. Citation: Yamada T, Hara K, Shojima N, Yamauchi T, Kadowaki T. Daytime napping and the risk of cardiovascular disease and all-cause mortality: a prospective study and

Napping, nighttime sleep, and cardiovascular risk factors in mid-life adults.

PubMed

Owens, Jane F; Buysse, Daniel J; Hall, Martica; Kamarck, Thomas W; Lee, Laisze; Strollo, Patrick J; Reis, Steven E; Matthews, Karen A

2010-08-15

To evaluate the relations between sleep characteristics and cardiovascular risk factors and napping behavior, and to assess whether daytime napping leads to subsequent better or worse sleep. The sample consisted of 224 (African American, Caucasian, and Asian) middle-aged men and women. Sleep measures included nine nights of actigraphy and sleep diaries, sleep questionnaires, and one night of polysomnography to measure sleep disordered breathing. More frequent napping was associated with shorter nighttime sleep duration averaged across the nine nights of actigraphy (especially among African Americans), more daytime sleepiness, more pain and fatigue by diary, and increased body mass index and waist circumference. Shorter nighttime sleep duration was associated with taking a nap during the next day and taking a nap was associated with less efficient sleep the next night. Napping in middle-aged men and women is associated with overall less nighttime sleep in African Americans and lower sleep efficiency as measured by actigraphy, and increased BMI and central adiposity. These findings point to the importance of measuring of napping in understanding associations of sleep with cardiovascular risk.

Effect of the raw material type and the reaction time on the synthesis of halloysite based Zeolite Na-P1

NASA Astrophysics Data System (ADS)

Meftah, Mahdi; Oueslati, Walid; Chorfi, Nejmeddine; Ben Haj Amara, Abdesslem

Zeolites are currently one of the most important classes of inorganic materials because of their multiple applications not only as ions exchangers and molecular sieves, but also as catalysts. This works focus the synthesis and the characterization of Zeolite Na-P1 using halloysite (collected near Ain Khemouda, western Tunisia) as the starting material. Two parameters, such as the host materials type (natural or treated) and the reaction time, involved in the synthesis process are investigated. The intermediate phases and final products were characterized by X-ray diffraction, Infrared IR spectroscopy, scanning electron microscopy and high-resolution 29Si and 27Al MAS NMR. Obtained results show that the hydrothermal synthesis from natural and heated-halloysite leads to formation of homogenous Zeolite Na-P1. The difference in the crystallization/transformation time process is explained by the effect of the dissolution rate of the starting materials in sodium hydroxide solution. In the case of heated halloysite, the synthesis reaction with alkali solution occurs very readily and achieved without prior thermal activation at high temperature. The optimal conditions of Zeolite Na-P1 crystallization, from heated-halloysite, are reached at 120 °C.

Night work and BMI: is it related to on-shift napping?

PubMed

Silva-Costa, Aline; Griep, Rosane Härter; Rotenberg, Lúcia

2017-11-17

On-shift napping can benefit night workers regarding sleep loss, synchronization of circadian rhythms, and alertness. However, few studies on napping can be found in the literature focused on possible health benefits. This cross-sectional study has investigated the role of on-shift napping on the association between night work and BMI in 409 night-shift nursing professionals. The number of working nights and the years of exposure to night work were significantly associated with increased BMI levels among non-nappers, but not among nappers. Results suggest a benefit of napping for weight gain, thus subsidizing occupational health policies on the regulation of on-shift napping among nursing workers.

SIRT3 restricts HBV transcription and replication via epigenetic regulation of cccDNA involving SUV39H1 and SETD1A histone methyltransferases.

PubMed

Ren, Ji-Hua; Hu, Jie-Li; Cheng, Sheng-Tao; Yu, Hai-Bo; Wong, Vincent Kam Wai; Law, Betty Yuen Kwan; Yang, Yong-Feng; Huang, Ying; Liu, Yi; Chen, Wei-Xian; Cai, Xue-Fei; Tang, Hua; Hu, Yuan; Zhang, Wen-Lu; Liu, Xiang; Long, Quan-Xin; Zhou, Li; Tao, Na-Na; Zhou, Hong-Zhong; Yang, Qiu-Xia; Ren, Fang; He, Lin; Gong, Rui; Huang, Ai-Long; Chen, Juan

2018-04-06

Hepatitis B virus (HBV) infection remains a major health problem worldwide. Maintenance of the covalently closed circular DNA (cccDNA) which serves as a template for HBV RNA transcription is responsible for the failure of eradicating chronic HBV during current antiviral therapy. cccDNA is assembled with cellular histone proteins into chromatin, but little is known about the regulation of HBV chromatin by histone posttranslational modifications. In this study, we identified SIRT3 as a host factor restricting HBV transcription and replication by screening seven members of Sirtuin family which is the class III histone deacetylase. Ectopic SIRT3 expression significantly reduced total HBV RNAs, 3.5-kb RNA as well as replicative intermediate DNA in HBV-infected HepG2-NTCP cells and PHH. In contrast, gene silencing of SIRT3 promoted HBV transcription and replication. Mechanistic study found nuclear SIRT3 was recruited to the HBV cccDNA, where it deacetylated histone 3 lysine 9 (H3K9). Importantly, occupancy of SIRT3 onto cccDNA could increase the recruitment of histone methyltransferase SUV39H1 to cccDNA and decrease recruitment of SETD1A, leading to a marked increase of H3K9me3 and a decrease of H3K4me3 on cccDNA. Moreover, SIRT3-mediated HBV cccDNA transcriptional repression involved decreased binding of host RNA polymerase II and transcription factor YY1 to cccDNA. Finally, viral protein HBx could relieve SIRT3-mediated cccDNA transcriptional repression by inhibiting both SIRT3 expression and its recruitment to cccDNA. SIRT3 is a novel host factor epigenetically restricting HBV cccDNA transcription by acting cooperatively with histone methyltransferase. These data provided a rational for the use of SIRT3 activators in the prevention or treatment of HBV infection. This article is protected by copyright. All rights reserved. © 2018 by the American Association for the Study of Liver Diseases.

High levels of histones promote whole-genome-duplications and trigger a Swe1WEE1-dependent phosphorylation of Cdc28CDK1.

PubMed

Maya Miles, Douglas; Peñate, Xenia; Sanmartín Olmo, Trinidad; Jourquin, Frederic; Muñoz Centeno, Maria Cruz; Mendoza, Manuel; Simon, Marie-Noelle; Chavez, Sebastian; Geli, Vincent

2018-03-27

Whole-genome duplications (WGDs) have played a central role in the evolution of genomes and constitute an important source of genome instability in cancer. Here, we show in Saccharomyces cerevisiae that abnormal accumulations of histones are sufficient to induce WGDs. Our results link these WGDs to a reduced incorporation of the histone variant H2A.Z to chromatin. Moreover, we show that high levels of histones promote Swe1 WEE1 stabilisation thereby triggering the phosphorylation and inhibition of Cdc28 CDK1 through a mechanism different of the canonical DNA damage response. Our results link high levels of histones to a specific type of genome instability that is quite frequently observed in cancer and uncovers a new mechanism that might be able to respond to high levels of histones. © 2018, Maya Miles et al.

EEG Changes Accompanying Successive Cycles of Sleep Restriction With and Without Naps in Adolescents

PubMed Central

Ong, Ju Lynn; Lo, June C.; Gooley, Joshua J.

2017-01-01

Abstract Study objectives: To investigate the temporal evolution of sleep EEG changes in adolescents across two cycles of sleep restriction and recovery simulating an intense school week and to examine the effect of an afternoon nap on nocturnal sleep. Methods: A parallel-group design, quasi-laboratory study was conducted in a student hostel. Fifty-seven adolescents (31 males, age = 15–19 years) were randomly assigned to nap or no nap groups. Participants underwent a 15-day protocol comprising two sleep restriction (5-hour time-in-bed [TIB]) and recovery (9-hour TIB) cycles. The nap group was also provided with a 1-hour nap opportunity at 14:00 following each sleep restriction night. Polysomnography recordings were obtained on nine nights and five nap episodes. Results: Naps reduced homeostatic sleep pressure on sleep restriction nights as evidenced by longer N2 latency and reduced total sleep time (TST), sleep efficiency (SE), and slow wave energy. Sleep debt accumulated in both groups, evidenced by increased TST, greater SE, and reduced wake after sleep onset on recovery compared to baseline nights. Changes were greater in the no nap group. Recovery sleep after the first cycle of sleep restriction did not restore sleep architecture to baseline in either group. SE, rapid eye movement (REM), and non-REM sleep increased, and N2 latency was reduced in the second sleep restriction period. Conclusions: Changes in sleep EEG induced by sleep restriction to 5-hour TIB for five nights were not eliminated after two nights of 9-hour recovery sleep. An afternoon nap helped but residual effects on the sleep EEG suggest that there is no substitute for adequate nocturnal sleep. PMID:28329386

Comparing the effects of nocturnal sleep and daytime napping on declarative memory consolidation.

PubMed

Lo, June C; Dijk, Derk-Jan; Groeger, John A

2014-01-01

Nocturnal sleep and daytime napping facilitate memory consolidation for semantically related and unrelated word pairs. We contrasted forgetting of both kinds of materials across a 12-hour interval involving either nocturnal sleep or daytime wakefulness (experiment 1) and a 2-hour interval involving either daytime napping or wakefulness (experiment 2). Beneficial effects of post-learning nocturnal sleep and daytime napping were greater for unrelated word pairs (Cohen's d=0.71 and 0.68) than for related ones (Cohen's d=0.58 and 0.15). While the size of nocturnal sleep and daytime napping effects was similar for unrelated word pairs, for related pairs, the effect of nocturnal sleep was more prominent. Together, these findings suggest that sleep preferentially facilitates offline memory processing of materials that are more susceptible to forgetting.

Napping and the risk of type 2 diabetes: a population-based prospective study.

PubMed

Hublin, Christer; Lehtovirta, Mikko; Partinen, Markku; Koskenvuo, Markku; Kaprio, Jaakko

2016-01-01

Some studies indicate an association between napping and increased risk of type 2 diabetes. We studied this prospectively in a sample representative of general population. A questionnaire was administered to the Finnish Twin Cohort in 1990 (response rate 77%, age 33-60 years). The study population included 12,244 subjects who replied to the question "Do you sleep during the daytime (take naps)?" with five response alternatives ranging from "no need" to "every or almost every day." Information on incident cases of diabetes was obtained by linkage to nationwide registers. Logistic regression models were used to obtain odds ratios (ORs) (95% confidence intervals) for incident type 2 diabetes risk in 1991-2004 by napping category. Adjustments were made for 11 socio-demographic and lifestyle covariates. For subjects aged 33-45 years at baseline, a questionnaire in 2011 provided information on prevalent diabetes. Thirty-four per cent had no need for napping, and 15% did so on ≥3 days weekly. There were 356 incident type 2 diabetes cases during the follow-up. Using the 'no need' category as the reference, the risk of type 2 diabetes was significantly increased only among those napping most frequently [OR 1.86 (1.29-2.67), age- and sex-adjusted]. After adjusting for other covariates, the results were essentially the same, but when adjusted for body mass index, the association decreased (to about 1.3) and was statistically non-significant. Analysis of 2011 self-reported type 2 diabetes was in line with the register data. Frequent napping is associated with future risk of type 2 diabetes. This association is largely explained by obesity. Copyright © 2015 Elsevier B.V. All rights reserved.

Compaction Kinetics on Single DNAs: Purified Nucleosome Reconstitution Systems versus Crude Extract

PubMed Central

Wagner, Gaudeline; Bancaud, Aurélien; Quivy, Jean-Pierre; Clapier, Cédric; Almouzni, Geneviève; Viovy, Jean-Louis

2005-01-01

Kinetics of compaction on single DNA molecules are studied by fluorescence videomicroscopy in the presence of 1), Xenopus egg extracts and 2), purified nucleosome reconstitution systems using a combination of histones with either the histone chaperone Nucleosome Assembly Protein (NAP-1) or negatively charged macromolecules such as polyglutamic acid and RNA. The comparison shows that the compaction rates can differ by a factor of up to 1000 for the same amount of histones, depending on the system used and on the presence of histone tails, which can be subjected to post-translational modifications. Reactions with purified reconstitution systems follow a slow and sequential mechanism, compatible with the deposition of one (H3-H4)2 tetramer followed by two (H2A-H2B) dimers. Addition of the histone chaperone NAP-1 increases both the rate of the reaction and the packing ratio of the final product. These stimulatory effects cannot be obtained with polyglutamic acid or RNA, suggesting that yNAP-1 impact on the reaction cannot simply be explained in terms of charge screening. Faster compaction kinetics and higher packing ratios are reproducibly reached with extracts, indicating a role of additional components present in this system. Data are discussed and models proposed to account for the kinetics obtained in our single-molecule assay. PMID:16100259

Histone chaperones: an escort network regulating histone traffic.

PubMed

De Koning, Leanne; Corpet, Armelle; Haber, James E; Almouzni, Geneviève

2007-11-01

In eukaryotes, DNA is organized into chromatin in a dynamic manner that enables it to be accessed for processes such as transcription and repair. Histones, the chief protein component of chromatin, must be assembled, replaced or exchanged to preserve or change this organization according to cellular needs. Histone chaperones are key actors during histone metabolism. Here we classify known histone chaperones and discuss how they build a network to escort histone proteins. Molecular interactions with histones and their potential specificity or redundancy are also discussed in light of chaperone structural properties. The multiplicity of histone chaperone partners, including histone modifiers, nucleosome remodelers and cell-cycle regulators, is relevant to their coordination with key cellular processes. Given the current interest in chromatin as a source of epigenetic marks, we address the potential contributions of histone chaperones to epigenetic memory and genome stability.

Night work and BMI: is it related to on-shift napping?

PubMed Central

Silva-Costa, Aline; Griep, Rosane Härter; Rotenberg, Lúcia

2017-01-01

ABSTRACT On-shift napping can benefit night workers regarding sleep loss, synchronization of circadian rhythms, and alertness. However, few studies on napping can be found in the literature focused on possible health benefits. This cross-sectional study has investigated the role of on-shift napping on the association between night work and BMI in 409 night-shift nursing professionals. The number of working nights and the years of exposure to night work were significantly associated with increased BMI levels among non-nappers, but not among nappers. Results suggest a benefit of napping for weight gain, thus subsidizing occupational health policies on the regulation of on-shift napping among nursing workers. PMID:29166450

Interferon regulatory factor 1 and histone H4 acetylation in systemic lupus erythematosus

PubMed Central

Leung, Yiu Tak; Shi, Lihua; Maurer, Kelly; Song, Li; Zhang, Zhe; Petri, Michelle; Sullivan, Kathleen E

2015-01-01

Histone acetylation modulates gene expression and has been described as increased in systemic lupus erythematosus (SLE). We investigated interferon regulatory factor 1 (IRF1) interactions that influence H4 acetylation (H4ac) in SLE. Intracellular flow cytometry for H4 acetylated lysine (K) 5, K8, K12, and K16 was performed. Histone acetylation was defined in monocytes and T cells from controls and SLE patients. RNA-Seq studies were performed on monocytes to look for an imbalance in histone acetyltransferases and histone deacetylase enzyme expression. Expression levels were validated using real-time quantitative RT-PCR. IRF1 induction of H4ac was evaluated using D54MG cells overexpressing IRF1. IRF1 protein interactions were studied using co-immunoprecipitation assays. IRF1-dependent recruitment of histone acetyltransferases to target genes was examined by ChIP assays using p300 antibody. Flow cytometry data showed significantly increased H4K5, H4K8, H4K12, and H4K16 acetylation in SLE monocytes. HDAC3 and HDAC11 gene expression were decreased in SLE monocytes. PCAF showed significantly higher gene expression in SLE than controls. IRF1-overexpressing D54MG cells were associated with significantly increased H4K5, H4K8, and H4K12 acetylation compared to vector-control D54MG cells both globally and at specific target genes. Co-immunoprecipitation studies using D54MG cells revealed IRF1 protein-protein interactions with PCAF, P300, CBP, GCN5, ATF2, and HDAC3. ChIP experiments demonstrated increased p300 recruitment to known IRF1 targets in D54MG cells overexpressing IRF1. In contrast, p300 binding to IRF1 targets decreased in D54MG cells with IRF1 knockdown. SLE appears to be associated with an imbalance in histone acetyltransferases and histone deacetylase enzymes favoring pathologic H4 acetylation. Furthermore, IRF1 directly interacts with chromatin modifying enzymes, supporting a model where recruitment to specific target genes is mediated in part by IRF1. PMID

Characterization of the Nencki Affective Picture System by discrete emotional categories (NAPS BE).

PubMed

Riegel, Monika; Żurawski, Łukasz; Wierzba, Małgorzata; Moslehi, Abnoss; Klocek, Łukasz; Horvat, Marko; Grabowska, Anna; Michałowski, Jarosław; Jednoróg, Katarzyna; Marchewka, Artur

2016-06-01

The Nencki Affective Picture System (NAPS; Marchewka, Żurawski, Jednoróg, & Grabowska, Behavior Research Methods, 2014) is a standardized set of 1,356 realistic, high-quality photographs divided into five categories (people, faces, animals, objects, and landscapes). NAPS has been primarily standardized along the affective dimensions of valence, arousal, and approach-avoidance, yet the characteristics of discrete emotions expressed by the images have not been investigated thus far. The aim of the present study was to collect normative ratings according to categorical models of emotions. A subset of 510 images from the original NAPS set was selected in order to proportionally cover the whole dimensional affective space. Among these, using three available classification methods, we identified images eliciting distinguishable discrete emotions. We introduce the basic-emotion normative ratings for the Nencki Affective Picture System (NAPS BE), which will allow researchers to control and manipulate stimulus properties specifically for their experimental questions of interest. The NAPS BE system is freely accessible to the scientific community for noncommercial use as supplementary materials to this article.

The association between daytime napping and risk of diabetes: a systematic review and meta-analysis of observational studies.

PubMed

Guo, Vivian Yawei; Cao, Bing; Wong, Carlos King Ho; Yu, Esther Yee Tak

2017-09-01

To investigate the association between daytime napping and prevalent/incident diabetes mellitus (DM) based on systematic review and meta-analytic data. The electronic databases of Embase, Medline, Pubmed and Web of Science were searched. Relevant studies were extracted by two reviewers independently. The associations between daytime napping (irrespective of duration), long nap (≥1 h/day) and short nap (<1 h/day), and risk of DM were assessed according to study types. Overall estimates were pooled using either fixed- or random-effect with inverse variance meta-analysis. Heterogeneity of included studies was assessed using the I 2 test and possible cause of the heterogeneity was examined by meta-regression analyses. Ten studies (four cross-sectional and six longitudinal cohort) comprising a total of 304,885 individuals and 20,857 cases of DM were included in the systematic review, with an average napping prevalence of 47%. Nappers were found to have increased risk of DM in both cross-sectional and cohort studies. However, significant heterogeneity was present. Long nap (≥1 h/day) was associated with both prevalent and incident DM; in particular, those with a daily nap over 1 h had a 31% increased risk of developing DM during follow-up (95% confidence interval: 2-67%). Conversely, no such association was found in individuals with short naps (<1 h/day) in cohort studies. Long daytime napping over 1 h per day was associated with increased risk of both prevalent and incident DM. Further studies are needed to confirm the findings. Copyright © 2017 Elsevier B.V. All rights reserved.

Napping, Nighttime Sleep, and Cardiovascular Risk Factors in Mid-Life Adults

PubMed Central

Owens, Jane F.; Buysse, Daniel J.; Hall, Martica; Kamarck, Thomas W.; Lee, Laisze; Strollo, Patrick J.; Reis, Steven E.; Matthews, Karen A.

2010-01-01

Study Objectives: To evaluate the relations between sleep characteristics and cardiovascular risk factors and napping behavior, and to assess whether daytime napping leads to subsequent better or worse sleep. Methods: The sample consisted of 224 (African American, Caucasian, and Asian) middle-aged men and women. Sleep measures included nine nights of actigraphy and sleep diaries, sleep questionnaires, and one night of polysomnography to measure sleep disordered breathing. Results: More frequent napping was associated with shorter nighttime sleep duration averaged across the nine nights of actigraphy (especially among African Americans), more daytime sleepiness, more pain and fatigue by diary, and increased body mass index and waist circumference. Shorter nighttime sleep duration was associated with taking a nap during the next day and taking a nap was associated with less efficient sleep the next night. Conclusions: Napping in middle-aged men and women is associated with overall less nighttime sleep in African Americans and lower sleep efficiency as measured by actigraphy, and increased BMI and central adiposity. These findings point to the importance of measuring of napping in understanding associations of sleep with cardiovascular risk. Citation: Owens JF; Buysee DJ; Hall M; Kamarck TW; Lee L; Strollo PJ; Reis SE; Matthews KA. Napping, nighttime sleep, and cardiovascular risk factors in mid-life adults. J Clin Sleep Med 2010;6(4):330-335. PMID:20726280

Activity-induced histone modifications govern Neurexin-1 mRNA splicing and memory preservation.

PubMed

Ding, Xinlu; Liu, Sanxiong; Tian, Miaomiao; Zhang, Wenhao; Zhu, Tao; Li, Dongdong; Wu, Jiawei; Deng, HaiTeng; Jia, Yichang; Xie, Wei; Xie, Hong; Guan, Ji-Song

2017-05-01

Epigenetic mechanisms regulate the formation, consolidation and reconsolidation of memories. However, the signaling path from neuronal activation to epigenetic modifications within the memory-related brain circuit remains unknown. We report that learning induces long-lasting histone modifications in hippocampal memory-activated neurons to regulate memory stability. Neuronal activity triggers a late-onset shift in Nrxn1 splice isoform choice at splicing site 4 by accumulating a repressive histone marker, H3K9me3, to modulate the splicing process. Activity-dependent phosphorylation of p66α via AMP-activated protein kinase recruits HDAC2 and Suv39h1 to establish repressive histone markers and changes the connectivity of the activated neurons. Removal of Suv39h1 abolished the activity-dependent shift in Nrxn1 splice isoform choice and reduced the stability of established memories. We uncover a cell-autonomous process for memory preservation in which memory-related neurons initiate a late-onset reduction of their rewiring capacities through activity-induced histone modifications.

JNK1 regulates histone acetylation in trigeminal neurons following chemical stimulation

PubMed Central

Wu, Jing; Zhang, Xuan; Nauta, Haring J; Lin, Qing; Li, Junfa; Fang, Li

2008-01-01

Trigeminal nerve fibers in nasal and oral cavities are sensitive to various environmental hazardous stimuli, which trigger many neurotoxic problems such as chronic migraine headache and trigeminal irritated disorders. However, the role of JNK kinase cascade and its epigenetic modulation of histone remodeling in trigeminal ganglion (TG) neurons activated by environmental neurotoxins remains unknown. Here we investigated the role of JNK/c-Jun cascade in the regulation of acetylation of H3 histone in TG neurons following in vitro stimulation by a neuro-inflammatory agent, mustard oil (MO). We found that MO stimulation elicited JNK/c-Jun pathway significantly by enhancing phospho-JNK1, phospho-c-Jun expression, and c-Jun activity, which were correlated with an elevated acetylated H3 histone in TG neurons. However, increases in phospho-c-Jun and c-Jun activity were significantly blocked by a JNK inhibitor, SP600125. We also found that altered H3 histone remodeling, assessed by H3 acetylation in triggered TG neurons, was reduced by SP600125. The study suggests that the activated JNK signaling in regulation of histone remodeling may contribute to neuro-epigentic changes in peripheral sensory neurons following environmental neurotoxic exposure. PMID:18822271

Napping: A public health issue. From epidemiological to laboratory studies.

PubMed

Faraut, Brice; Andrillon, Thomas; Vecchierini, Marie-Françoise; Leger, Damien

2017-10-01

Sleep specialists have proposed measures to counteract the negative short- and long-term consequences of sleep debt, and some have suggested the nap as a potential and powerful "public health tool". Here, we address this countermeasure aspect of napping viewed as an action against sleep deprivation rather than an action associated with poor health. We review the physiological functions that have been associated positively with napping in both public health and clinical settings (sleep-related accidents, work and school, and cardiovascular risk) and in laboratory-based studies with potential public health issues (cognitive performance, stress, immune function and pain sensitivity). We also discuss the circumstances in which napping-depending on several factors, including nap duration, frequency, and age-could be a potential public health tool and a countermeasure for sleep loss in terms of reducing accidents and cardiovascular events and improving sleep-restriction-sensitive working performance. However, the impact of napping and the nature of the sleep stage(s) involved still need to be evaluated, especially from the perspective of coping strategies in populations with chronic sleep debt, such as night and shift workers. Copyright © 2016 Elsevier Ltd. All rights reserved.

Napping and the Selective Consolidation of Negative Aspects of Scenes

PubMed Central

Payne, Jessica D.; Kensinger, Elizabeth A.; Wamsley, Erin; Spreng, R. Nathan; Alger, Sara; Gibler, Kyle; Schacter, Daniel L.; Stickgold, Robert

2018-01-01

After information is encoded into memory, it undergoes an offline period of consolidation that occurs optimally during sleep. The consolidation process not only solidifies memories, but also selectively preserves aspects of experience that are emotionally salient and relevant for future use. Here, we provide evidence that an afternoon nap is sufficient to trigger preferential memory for emotional information contained in complex scenes. Selective memory for negative emotional information was enhanced after a nap compared to wakefulness in two control conditions designed to carefully address interference and time-of-day confounds. Although prior evidence has connected negative emotional memory formation to rapid eye movement (REM) sleep physiology, we found that non-REM delta activity and the amount of slow wave sleep (SWS) in the nap were robustly related to the selective consolidation of negative information. These findings suggest that the mechanisms underlying memory consolidation benefits associated with napping and nighttime sleep are not always the same. Finally, we provide preliminary evidence that the magnitude of the emotional memory benefit conferred by sleep is equivalent following a nap and a full night of sleep, suggesting that selective emotional remembering can be economically achieved by taking a nap. PMID:25706830

Self-Reported Napping Behavior Change After Continuous Positive Airway Pressure Treatment in Older Adults with Obstructive Sleep Apnea.

PubMed

Hsieh, Cheng-Fang; Riha, Renata L; Morrison, Ian; Hsu, Chung-Yao

2016-08-01

To assess the effect of continuous positive airway pressure (CPAP) on napping behavior in adults aged 60 and older with obstructive sleep apnea-hypopnea syndrome (OSAHS). Retrospective cohort study using questionnaires. Sleep center. Individuals starting CPAP treatment between April 2010 and March 2012 (mean age 65.2 ± 4.7; M:F = 3.9:1; N = 107). All subjects underwent sleep studies, clinical reviews, and CPAP adherence checks and completed a questionnaire regarding CPAP adherence, current employment status, sleep patterns before and after CPAP, and factors affecting their current sleep patterns. CPAP treatment duration was 82.7 ± 30.0 weeks, and objective adherence was 5.4 ± 2.0 hours per night overall. Daytime nap frequency before CPAP treatment was higher in those with a history of stroke or cardiovascular disease. Both sexes had a significant reduction in daytime napping (men, P < .001; women, P = .008), evening napping (men, P < .001; women, P = .02), and daily nap duration (men, P < .001; women, P = .02). Logistic regression analysis showed that the reduction in self-reported daily nap duration was associated with younger age (odds ratio (OR) = 0.86, P = .04), a decrease in ESS score (OR = 1.20, P = .03), and longer self-reported daily nap duration at baseline (OR = 31.52, P < .001). Long-term CPAP treatment in older adults with OSAHS can play a significant role in reducing nap frequency and daily nap duration. Aging or shorter baseline daily nap duration may attenuate this effect. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

Structural Investigations of the Nickel-Induced Inhibition of Truncated Constructs of the JMJD2 Family of Histone Demethylases Using X-ray Absorption Spectroscopy

PubMed Central

Giri, Nitai Charan; Passantino, Lisa; Sun, Hong; Zoroddu, Maria Antonietta; Costa, Max; Maroney, Michael J.

2013-01-01

Occupational and/or environmental exposure to nickel has been implicated in various types of cancer, and in vitro exposure to nickel compounds results in accumulation of Ni(II) ions in cells. One of the major targets of Ni(II) ions inside the cell is Fe(II)- and αKG-dependent dioxygenases. Using JMJD2A and JMJD2C as examples, we show that JMJD2 family of histone demethylases, which are products of putative oncogenes as well as Fe(II)- and αKG-dependent dioxygenases, are highly sensitive to inhibition by Ni(II) ions. In this work, X-ray absorption spectroscopy (XAS) has been used to investigate the Fe(II) active site of truncated JMJD2A and JMJD2C (1 – 350 aa) in the presence and absence of αKG and/or substrate to obtain mechanistic details of the early steps in catalysis that precede O2 binding in histone demethylation by the JMJD2 family of histone demethylases. Zinc K-edge XAS has been performed on the resting JMJD2A (with iron in the active site) to confirm the presence of the expected structural zinc site. XAS of the Ni(II)-substituted enzymes has also been performed to investigate the inhibition of these enzymes by Ni(II) ions. Our XAS results indicate that the five-coordinate Fe(II) center in the resting enzyme is retained in the binary and ternary complexes. In contrast, the Ni(II) center is six-coordinate in the resting enzyme, binary and ternary complexes. XAS results indicate that both Fe(II) and Ni(II) bind αKG in the binary and ternary complexes. The electron density build-up that is observed at the Fe(II) center in the presence of αKG and substrate is not observed at the Ni(II) center. Thus, both electronic and steric factors are responsible for Ni-induced inhibition of the JMJD2 family of histone demethylases. Ni-induced inhibition of these enzymes may explain the alteration of the epigenetic mechanism of gene expression that is responsible for Ni-induced carcinogenesis. PMID:23692052

EEG Changes Accompanying Successive Cycles of Sleep Restriction With and Without Naps in Adolescents.

PubMed

Ong, Ju Lynn; Lo, June C; Gooley, Joshua J; Chee, Michael W L

2017-04-01

To investigate the temporal evolution of sleep EEG changes in adolescents across two cycles of sleep restriction and recovery simulating an intense school week and to examine the effect of an afternoon nap on nocturnal sleep. A parallel-group design, quasi-laboratory study was conducted in a student hostel. Fifty-seven adolescents (31 males, age = 15-19 years) were randomly assigned to nap or no nap groups. Participants underwent a 15-day protocol comprising two sleep restriction (5-hour time-in-bed [TIB]) and recovery (9-hour TIB) cycles. The nap group was also provided with a 1-hour nap opportunity at 14:00 following each sleep restriction night. Polysomnography recordings were obtained on nine nights and five nap episodes. Naps reduced homeostatic sleep pressure on sleep restriction nights as evidenced by longer N2 latency and reduced total sleep time (TST), sleep efficiency (SE), and slow wave energy. Sleep debt accumulated in both groups, evidenced by increased TST, greater SE, and reduced wake after sleep onset on recovery compared to baseline nights. Changes were greater in the no nap group. Recovery sleep after the first cycle of sleep restriction did not restore sleep architecture to baseline in either group. SE, rapid eye movement (REM), and non-REM sleep increased, and N2 latency was reduced in the second sleep restriction period. Changes in sleep EEG induced by sleep restriction to 5-hour TIB for five nights were not eliminated after two nights of 9-hour recovery sleep. An afternoon nap helped but residual effects on the sleep EEG suggest that there is no substitute for adequate nocturnal sleep. © Sleep Research Society 2017. Published by Oxford University Press [on behalf of the Sleep Research Society].

Integrated synthesis of zeolites 4A and Na-P1 using coal fly ash for application in the formulation of detergents and swine wastewater treatment.

PubMed

Cardoso, Ariela M; Horn, Martha B; Ferret, Lizete S; Azevedo, Carla M N; Pires, Marçal

2015-04-28

Several researchers have reported zeolite synthesis using coal ash for a wide range of applications. However, little attention has been given to green processes, including moderate synthesis conditions, using waste as raw material and effluent reuse or reduction. In this study, Brazilian coal fly ashes were used for integrated synthesis of zeolites 4A and Na-P1 by two different routes and under moderate operating conditions (temperature and pressure). Both procedures produced zeolites with similar conversions (zeolite 4A at 82% purity and zeolite Na-P1 at 57-61%) and high CEC values (zeolites 4A: 4.5meqCa(2+)g(-1) and zeolites Na-P1: 2.6-2.8meqNH4(+)g(-1)). However, process 1 generated less effluent for the zeolite mass produced (7mLg(-1)), with low residual Si and Al levels and 74% of the Si available in the coal fly ash incorporated into the zeolite, while only 55% is used in process 2. For use as a builder in detergents, synthetic zeolite 4A exhibited conformity parameters equal to or greater than those of the commercial zeolite adopted as reference. Treatment of swine wastewater with zeolite Na-P1 resulted in a high removal capacity for total ammoniacal nitrogen (31mgg(-1)). Copyright © 2015 Elsevier B.V. All rights reserved.

Comparing the Effects of Nocturnal Sleep and Daytime Napping on Declarative Memory Consolidation

PubMed Central

Lo, June C.; Dijk, Derk-Jan; Groeger, John A.

2014-01-01

Nocturnal sleep and daytime napping facilitate memory consolidation for semantically related and unrelated word pairs. We contrasted forgetting of both kinds of materials across a 12-hour interval involving either nocturnal sleep or daytime wakefulness (experiment 1) and a 2-hour interval involving either daytime napping or wakefulness (experiment 2). Beneficial effects of post-learning nocturnal sleep and daytime napping were greater for unrelated word pairs (Cohen’s d = 0.71 and 0.68) than for related ones (Cohen’s d = 0.58 and 0.15). While the size of nocturnal sleep and daytime napping effects was similar for unrelated word pairs, for related pairs, the effect of nocturnal sleep was more prominent. Together, these findings suggest that sleep preferentially facilitates offline memory processing of materials that are more susceptible to forgetting. PMID:25229457

Epigenetic Regulation of the NR4A Orphan Nuclear Receptor NOR1 By Histone Acetylation

PubMed Central

Zhao, Yue; Nomiyama, Takashi; Findeisen, Hannes M.; Qing, Hua; Aono, Jun; Jones, Karrie L.; Heywood, Elizabeth B.; Bruemmer, Dennis

2014-01-01

The nuclear receptor NOR1 is an immediate-early response gene implicated in the transcriptional control of proliferation. Since the expression level of NOR1 is rapidly induced through cAMP response element binding (CREB) protein-dependent promoter activation, we investigated the contribution of histone acetylation to this transient induction. We demonstrate that NOR1 transcription is induced by histone deacetylase (HDAC) inhibition and by depletion of HDAC1 and HDAC3. HDAC inhibition activated the NOR1 promoter, increased histone acetylation and augmented the recruitment of phosphorylated CREB to the promoter. Furthermore, HDAC inhibition increased Ser133 phosphorylation of CREB and augmented NOR1 protein stability. These data outline previously unrecognized mechanisms of NOR1 regulation and illustrate a key role for histone acetylation in the rapid induction of NOR1. PMID:25451221

Transcriptional Regulation of JARID1B/KDM5B Histone Demethylase by Ikaros, Histone Deacetylase 1 (HDAC1), and Casein Kinase 2 (CK2) in B-cell Acute Lymphoblastic Leukemia*

PubMed Central

Wang, Haijun; Song, Chunhua; Ding, Yali; Pan, Xiaokang; Ge, Zheng; Tan, Bi-Hua; Gowda, Chandrika; Sachdev, Mansi; Muthusami, Sunil; Ouyang, Hongsheng; Lai, Liangxue; Francis, Olivia L.; Morris, Christopher L.; Abdel-Azim, Hisham; Dorsam, Glenn; Xiang, Meixian; Payne, Kimberly J.; Dovat, Sinisa

2016-01-01

Impaired function of the Ikaros (IKZF1) protein is associated with the development of high-risk B-cell precursor acute lymphoblastic leukemia (B-ALL). The mechanisms of Ikaros tumor suppressor activity in leukemia are unknown. Ikaros binds to the upstream regulatory elements of its target genes and regulates their transcription via chromatin remodeling. Here, we report that Ikaros represses transcription of the histone H3K4 demethylase, JARID1B (KDM5B). Transcriptional repression of JARID1B is associated with increased global levels of H3K4 trimethylation. Ikaros-mediated repression of JARID1B is dependent on the activity of the histone deacetylase, HDAC1, which binds to the upstream regulatory element of JARID1B in complex with Ikaros. In leukemia, JARID1B is overexpressed, and its inhibition results in cellular growth arrest. Ikaros-mediated repression of JARID1B in leukemia is impaired by pro-oncogenic casein kinase 2 (CK2). Inhibition of CK2 results in increased binding of the Ikaros-HDAC1 complex to the promoter of JARID1B, with increased formation of trimethylated histone H3 lysine 27 and decreased histone H3 Lys-9 acetylation. In cases of high-risk B-ALL that carry deletion of one Ikaros (IKZF1) allele, targeted inhibition of CK2 restores Ikaros binding to the JARID1B promoter and repression of JARID1B. In summary, the presented data suggest a mechanism through which Ikaros and HDAC1 regulate the epigenetic signature in leukemia: via regulation of JARID1B transcription. The presented data identify JARID1B as a novel therapeutic target in B-ALL and provide a rationale for the use of CK2 inhibitors in the treatment of high-risk B-ALL. PMID:26655717

Long-Term Single and Joint Effects of Excessive Daytime Napping on the HOMA-IR Index and Glycosylated Hemoglobin

PubMed Central

Li, Xue; Pang, Xiuyu; Zhang, Qiao; Qu, Qiannuo; Hou, Zhigang; Liu, Zhipeng; Lv, Lin; Na, Guanqiong; Zhang, Wei; Sun, Changhao; Li, Ying

2016-01-01

Abstract This prospective cohort study was conducted to assess the duration of daytime napping and its effect combined with night sleep deprivation on the risk of developing high HOMA-IR (homeostasis model assessment of insulin resistance) index and disadvantageous changes in glycosylated hemoglobin (HbA1c) levels. A total of 5845 diabetes-free subjects (2736 women and 3109 men), 30 to 65 years of age, were targeted for this cohort study since 2008. Multiple adjusted Cox regression models were performed to evaluate the single and joint effects of daytime napping on the risk of an elevated HbA1c level and high HOMA-IR index. After an average of 4.5 years of follow-up, >30 minutes of daytime napping was significantly associated with an increased risk of an elevated HbA1c level (>6.5%) in men and women (all P trend < 0.05). Hazard ratios (HRs) for an HbA1c level between 5.7% and 6.4% were also significant in the entire cohort and women, but nonsignificant in men. HRs (95% confidence interval, CIs) for the high HOMA-IR index in the entire cohort, men, and women were 1.33 (1.10–1.62), 1.46 (1.08–1.98), and 1.47 (1.12–1.91), respectively. The combination of sleep deprivation with no naps or >30 minutes napping and the combination of no sleep deprivation with >30 minutes daytime napping were all associated with an HbA1c level >6.5% (HR = 2.08, 95% CI = 1.24–3.51; HR = 4.00, 95% CI = 2.03–7.90; and HR = 2.05, 95% CI = 1.29–3.27, respectively). No sleep deprivation combined with >30 minutes daytime napping correlated with a high risk of an HbA1c level between 5.7% and 6.4% and high HOMA-IR index (HR = 2.12, 95% CI = 1.48–3.02; and HR = 1.35, 95% CI = 1.10–1.65, respectively). Daytime napping >30 minutes was associated with a high risk of an elevated HbA1c level and high HOMA-IR index. No sleep deprivation combined with napping >30 minutes carries a risk of abnormal glucose metabolism. Sleep deprivation combined with

New common program requirements for the resident physician workforce and the omission of strategic napping: A missed opportunity.

PubMed

Shnayder, Michelle M; St Onge, Joan E; Caban-Martinez, Alberto J

2017-09-01

Napping has known benefits for fatigue mitigation and improved alertness. However the Accreditation Council for Graduate Medical Education (ACGME) New Common Program Requirements recently removed the 16 h work limit for PGY1 residents and removed any suggestions of napping. We utilized a cross-sectional study design to administer a 44-item questionnaire in June 2016 to 858 residents and fellows at one large urban academic medical center. We assessed: 1) resident physician sentiment of work environment supportiveness for napping at work; and 2) agreement with 2011 ACGME guidelines on workweek hour limitations and strategic napping recommendations. While 89% of residents reported access to an on-call room at work, only 20% felt their work environment supported a culture of napping while at work. Over 76% expressed agreement with the 2011 ACGME work-hour restrictions. Strategies to support napping and well-being within the resident physician workforce and organizational setting are warranted. © 2017 Wiley Periodicals, Inc.

Insufficient sleep in young patients with diabetes and their families.

PubMed

Estrada, Carmela L; Danielson, Kirstie K; Drum, Melinda L; Lipton, Rebecca B

2012-01-01

We examined sleep in families of individuals with type 1 diabetes and the relationship of sleep with obesity, diabetes, and insulin resistance. Probands with type 1 diabetes diagnosed before age 18 and first- and second-degree relatives were included (n = 323). Demographic, anthropometric and clinical variables, and self-reported sleep duration and napping were assessed. On average, adults (≥20 years) slept 7.5 (SD 1.5) hr, whereas children (5-11 years) and adolescents (12-19 years) slept 9.8 (SD 1.1) and 8.5 (SD 1.9) hr, respectively (p < .01). Based on national recommendations, 40.9% of participants slept insufficiently, particularly young people (vs. adults, p < .01). In age-group stratified analysis, there were no significant associations of insufficient sleep or sleep duration with obesity, diabetes status, or insulin resistance after adjustment for age, race/ethnicity, and gender. In all, 42% of participants reported napping regularly (≥1/week), with adolescents significantly more likely to do so (vs. adults, odds ratio [OR] = 1.95, p < .01). Non-Hispanic Blacks and Hispanics also had higher odds of regular napping (vs. non-Hispanic Whites, OR = 3.74, p < .01 and OR = 2.52, p = .03, respectively). In adjusted analysis, leaner (vs. obese) adolescents, whether measured by body mass index, percentage body fat, or waist circumference, were significantly more likely to nap regularly. We found that insufficient sleep was significantly more likely in children and adolescents compared with adults in families with type 1 diabetes. Lower adiposity was associated with regular napping in adolescents. The high prevalence of insufficient sleep in young patients with type 1 diabetes and their relatives detected in the current study may have significant health consequences.

Mapping the local protein interactome of the NuA3 histone acetyltransferase

PubMed Central

Smart, Sherri K; Mackintosh, Samuel G; Edmondson, Ricky D; Taverna, Sean D; Tackett, Alan J

2009-01-01

Protein–protein interactions modulate cellular functions ranging from the activity of enzymes to signal transduction cascades. A technology termed transient isotopic differentiation of interactions as random or targeted (transient I-DIRT) is described for the identification of stable and transient protein–protein interactions in vivo. The procedure combines mild in vivo chemical cross-linking and non-stringent affinity purification to isolate low abundance chromatin-associated protein complexes. Using isotopic labeling and mass spectrometric readout, purified proteins are categorized with respect to the protein ‘bait’ as stable, transient, or contaminant. Here we characterize the local interactome of the chromatin-associated NuA3 histone lysine-acetyltransferase protein complex. We describe transient associations with the yFACT nucleosome assembly complex, RSC chromatin remodeling complex and a nucleosome assembly protein. These novel, physical associations with yFACT, RSC, and Nap1 provide insight into the mechanism of NuA3-associated transcription and chromatin regulation. PMID:19621382

Daytime Napping and the Risk of All-Cause and Cause-Specific Mortality: A 13-Year Follow-up of a British Population

PubMed Central

Leng, Yue; Wainwright, Nick W. J.; Cappuccio, Francesco P.; Surtees, Paul G.; Hayat, Shabina; Luben, Robert; Brayne, Carol; Khaw, Kay-Tee

2014-01-01

Epidemiologic studies have reported conflicting results on the relationship between daytime napping and mortality risk, and there are few data on the potential association in the British population. We investigated the associations between daytime napping and all-cause or cause-specific mortality in the European Prospective Investigation Into Cancer-Norfolk study, a British population-based cohort study. Among the 16,374 men and women who answered questions on napping habits between 1998 and 2000, a total of 3,251 died during the 13-year follow-up. Daytime napping was associated with an increased risk of all-cause mortality (for napping less than 1 hour per day on average, hazard ratio = 1.14, 95% confidence interval: 1.02, 1.27; for napping 1 hour or longer per day on average, hazard ratio = 1.32, 95% confidence interval: 1.04, 1.68), independent of age, sex, social class, educational level, marital status, employment status, body mass index, physical activity level, smoking status, alcohol intake, depression, self-reported general health, use of hypnotic drugs or other medications, time spent in bed at night, and presence of preexisting health conditions. This association was more pronounced for death from respiratory diseases (for napping less than 1 hour, hazard ratio = 1.40, 95% confidence interval: 0.95, 2.05; for napping 1 hour or more, hazard ratio = 2.56, 95% confidence interval: 1.34, 4.86) and in individuals 65 years of age or younger. Excessive daytime napping might be a useful marker of underlying health risk, particularly of respiratory problems, especially among those 65 years of age or younger. Further research is required to clarify the nature of the observed association. PMID:24685532

Daytime napping and the risk of all-cause and cause-specific mortality: a 13-year follow-up of a British population.

PubMed

Leng, Yue; Wainwright, Nick W J; Cappuccio, Francesco P; Surtees, Paul G; Hayat, Shabina; Luben, Robert; Brayne, Carol; Khaw, Kay-Tee

2014-05-01

Epidemiologic studies have reported conflicting results on the relationship between daytime napping and mortality risk, and there are few data on the potential association in the British population. We investigated the associations between daytime napping and all-cause or cause-specific mortality in the European Prospective Investigation Into Cancer-Norfolk study, a British population-based cohort study. Among the 16,374 men and women who answered questions on napping habits between 1998 and 2000, a total of 3,251 died during the 13-year follow-up. Daytime napping was associated with an increased risk of all-cause mortality (for napping less than 1 hour per day on average, hazard ratio = 1.14, 95% confidence interval: 1.02, 1.27; for napping 1 hour or longer per day on average, hazard ratio = 1.32, 95% confidence interval: 1.04, 1.68), independent of age, sex, social class, educational level, marital status, employment status, body mass index, physical activity level, smoking status, alcohol intake, depression, self-reported general health, use of hypnotic drugs or other medications, time spent in bed at night, and presence of preexisting health conditions. This association was more pronounced for death from respiratory diseases (for napping less than 1 hour, hazard ratio = 1.40, 95% confidence interval: 0.95, 2.05; for napping 1 hour or more, hazard ratio = 2.56, 95% confidence interval: 1.34, 4.86) and in individuals 65 years of age or younger. Excessive daytime napping might be a useful marker of underlying health risk, particularly of respiratory problems, especially among those 65 years of age or younger. Further research is required to clarify the nature of the observed association.

Nap polygraphic recordings after partial sleep deprivation in patients with suspected epileptic seizures.

PubMed

Peraita-Adrados, R; Gutierrez-Solana, L; Ruiz-Falcó, M L; García-Peñas, J J

2001-02-01

A review of the literature shows that nap recordings make a significant contribution to epilepsy studies, providing evidence of specific EEG findings in patients suspected of having epilepsy. In addition, sleep deprivation can cause paroxysmal EEG activity and clinical seizures. We studied retrospectively 686 patients, 51.8% males and 48.2% females, who had experienced at least one episode classified from the clinical point of view as epileptic in origin. They were divided into six age groups. Patients underwent a two-hour (1 P.M.-3 P.M.) nap-video-polygraphic recording (EEG 13 channels using the standard 10-20 system, EOG, ECG, EMG and respiration), following a partial sleep deprivation (1 to 3 h) the night before. A second recording was made in 40 patients. In 35.3% of patients, a complete sleep cycle was obtained; in 64.6% sufficient light and deep NREM sleep was obtained, but not REM stage; in 9.3%, we only observed drowsiness and stage 1 of sleep, and this group was excluded from the analysis. Interictal and/or ictal epileptic discharges were observed during the first nap recording in 245 patients (40.4% of the sample). In addition, in 40 patients (11%) with normal or inconclusive first nap EEG, a second recording was able to demonstrate epileptic abnormalities in 35% of cases. Because of its good cost/benefit ratio and availability in most western laboratories, we consider the 'nap plus partial sleep deprivation' method as advantageous over other activation procedures.

Citrullination regulates pluripotency and histone H1 binding to chromatin

NASA Astrophysics Data System (ADS)

Christophorou, Maria A.; Castelo-Branco, Gonçalo; Halley-Stott, Richard P.; Oliveira, Clara Slade; Loos, Remco; Radzisheuskaya, Aliaksandra; Mowen, Kerri A.; Bertone, Paul; Silva, José C. R.; Zernicka-Goetz, Magdalena; Nielsen, Michael L.; Gurdon, John B.; Kouzarides, Tony

2014-03-01

Citrullination is the post-translational conversion of an arginine residue within a protein to the non-coded amino acid citrulline. This modification leads to the loss of a positive charge and reduction in hydrogen-bonding ability. It is carried out by a small family of tissue-specific vertebrate enzymes called peptidylarginine deiminases (PADIs) and is associated with the development of diverse pathological states such as autoimmunity, cancer, neurodegenerative disorders, prion diseases and thrombosis. Nevertheless, the physiological functions of citrullination remain ill-defined, although citrullination of core histones has been linked to transcriptional regulation and the DNA damage response. PADI4 (also called PAD4 or PADV), the only PADI with a nuclear localization signal, was previously shown to act in myeloid cells where it mediates profound chromatin decondensation during the innate immune response to infection. Here we show that the expression and enzymatic activity of Padi4 are also induced under conditions of ground-state pluripotency and during reprogramming in mouse. Padi4 is part of the pluripotency transcriptional network, binding to regulatory elements of key stem-cell genes and activating their expression. Its inhibition lowers the percentage of pluripotent cells in the early mouse embryo and significantly reduces reprogramming efficiency. Using an unbiased proteomic approach we identify linker histone H1 variants, which are involved in the generation of compact chromatin, as novel PADI4 substrates. Citrullination of a single arginine residue within the DNA-binding site of H1 results in its displacement from chromatin and global chromatin decondensation. Together, these results uncover a role for citrullination in the regulation of pluripotency and provide new mechanistic insights into how citrullination regulates chromatin compaction.

Nurse managers' perception of night-shift napping: A cross-sectional survey.

PubMed

Dalky, Heyam F; Raeda, AbuAlRub F; Esraa, Aldalqamouni A

2017-10-04

Night-shift work often results in sleep deprivation, and this in turn results in fatigue that jeopardizes both nurse and patient safety. Napping is considered a viable deterrent to fatigue, yet hospital administration has been slow to adopt napping. To identify nurse managers' knowledge and approval of napping practices for nurses on night shifts. Nurse managers at nine Jordanian hospitals (n = 129) were surveyed using an Arabic version of a questionnaire previously used in a Canadian study. Descriptive statistics were used to describe results, and a one-way ANOVA was used to determine if relationships existed among nurse manager's approval of napping and nurse demographic characteristics. The majority of nurse managers (61%) knew nurses were napping during breaks. However, the managers reported there was no written policy for napping. A majority thought there were more benefits to napping than drawbacks. Some 55% of nurse managers recognized fatigue as a cause of errors or incidents regarding patient safety, and 40% perceived fatigue to be a factor in staff injuries. This study supports an urgent need for shared responsibility among nursing administration, and bedside nurses to develop evidence-based programs to counteract the effects of nurse fatigue. © 2017 Wiley Periodicals, Inc.

Glutathione-S-transferase pi 1(GSTP1) gene silencing in prostate cancer cells is reversed by the histone deacetylase inhibitor depsipeptide.

PubMed

Hauptstock, Vera; Kuriakose, Sapuna; Schmidt, Doris; Düster, Robert; Müller, Stefan C; von Ruecker, Alexander; Ellinger, Jörg

2011-09-09

Gene silencing by epigenetic mechanisms is frequent in prostate cancer (PCA). The link between DNA hypermethylation and histone modifications is not completely understood. We chose the GSTP1 gene which is silenced by hypermethylation to analyze the effect of the histone deacetylase inhibitor depsipeptide on DNA methylation and histone modifications at the GSTP1 promoter site. Prostate cell lines (PC-3, LNCaP, and BPH-1) were treated with depsipeptide; apoptosis (FACS analysis), GSTP1 mRNA levels (quantitative real-time PCR), DNA hypermethylation (methylation-specific PCR), and histone modifications (chromatin immunoprecipitation) were studied. Depsipeptide induced apoptosis in PCA cells, but not a cell cycle arrest. Depispeptide reversed DNA hypermethylation and repressive histone modifications (reduction of H3K9me2/3 and H3K27me2/3; increase of H3K18Ac), thereby inducing GSTP1 mRNA re-expression. Successful therapy requires both, DNA demethylation and activating histone modifications, to induce complete gene expression of epigenetically silenced genes and depsipeptide fulfils both criteria. Copyright © 2011 Elsevier Inc. All rights reserved.

Molecular insights into the recognition of N-terminal histone modifications by the BRPF1 bromodomain

PubMed Central

Poplawski, Amanda; Hu, Kaifeng; Lee, Woonghee; Natesan, Senthil; Peng, Danni; Carlson, Samuel; Shi, Xiaobing; Balaz, Stefan; Markley, John L.; Glass, Karen C.

2014-01-01

The monocytic leukemic zinc-finger (MOZ) histone acetyltransferase (HAT) acetylates free histones H3, H4, H2A, and H2B in vitro and is associated with up-regulation of gene transcription. The MOZ HAT functions as a quaternary complex with the bromodomain-PHD finger protein 1 (BRPF1), inhibitor of growth 5 (ING5), and hEaf6 subunits. BRPF1 links the MOZ catalytic subunit to the ING5 and hEaf6 subunits, thereby promoting MOZ HAT activity. Human BRPF1 contains multiple effector domains with known roles in gene transcription, and chromatin binding and remodeling. However, the biological function of the BRPF1 bromodomain remains unknown. Our findings reveal novel interactions of the BRPF1 bromodomain with multiple acetyllysine residues on the N-terminus of histones, and show it preferentially selects for H2AK5ac, H4K12ac and H3K14ac. We used chemical shift perturbation data from NMR titration experiments to map the BRPF1 bromodomain ligand binding pocket and identified key residues responsible for coordination of the post-translationally modified histones. Extensive molecular dynamics simulations were used to generate structural models of bromodomain-histone ligand complexes, to analyze H-bonding and other interactions, and to calculate the binding free energies. Our results outline the molecular mechanism driving binding specificity of the BRPF1 bromodomain for discrete acetyllysine residues on the N-terminal histone tails. Together these data provide insights on how histone recognition by the bromodomain directs the biological function of BRPF1, ultimately targeting the MOZ HAT complex to chromatin substrates. PMID:24333487

Class I Histone Deacetylase HDAC1 and WRN RECQ Helicase Contribute Additively to Protect Replication Forks upon Hydroxyurea-induced Arrest.

PubMed

Kehrli, Keffy; Phelps, Michael; Lazarchuk, Pavlo; Chen, Eleanor; Monnat, Ray; Sidorova, Julia M

2016-11-18

The WRN helicase/exonuclease is mutated in Werner syndrome of genomic instability and premature aging. WRN-depleted fibroblasts, although remaining largely viable, have a reduced capacity to maintain replication forks active during a transient hydroxyurea-induced arrest. A strand exchange protein, RAD51, is also required for replication fork maintenance, and here we show that recruitment of RAD51 to stalled forks is reduced in the absence of WRN. We performed a siRNA screen for genes that are required for viability of WRN-depleted cells after hydroxyurea treatment, and identified HDAC1, a member of the class I histone deacetylase family. One of the functions of HDAC1, which it performs together with a close homolog HDAC2, is deacetylation of new histone H4 deposited at replication forks. We show that HDAC1 depletion exacerbates defects in fork reactivation and progression after hydroxyurea treatment observed in WRN- or RAD51-deficient cells. The additive WRN, HDAC1 loss-of-function phenotype is also observed with a catalytic mutant of HDAC1; however, it does not correlate with changes in histone H4 deacetylation at replication forks. On the other hand, inhibition of histone deacetylation by an inhibitor specific to HDACs 1-3, CI-994, correlates with increased processing of newly synthesized DNA strands in hydroxyurea-stalled forks. WRN co-precipitates with HDAC1 and HDAC2. Taken together, our findings indicate that WRN interacts with HDACs 1 and 2 to facilitate activity of stalled replication forks under conditions of replication stress. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Self-reported Napping, Sleep Duration and Quality in the Lifestyle Interventions and Independence for Elders Pilot (LIFE-P) Study

PubMed Central

Picarsic, Jennifer L.; Glynn, Nancy W.; Taylor, Christopher A.; Katula, Jeffery; Goldman, Suzanne E.; Studenski, Stephanie; Newman, Anne B.

2010-01-01

OBJECTIVES To determine the prevalence of self-reported napping and its association with subjective nighttime sleep duration and quality, as measured by sleep-onset latency and sleep efficiency. DESIGN Cross-sectional study. SETTING Lifestyle Interventions and Independence for Elder’s Pilot Study. PARTICIPANTS Community-dwelling older adults (N=414), aged 70 to 89 years. MEASUREMENTS Self-report questionnaire on napping and sleep, derived from the Pittsburgh Sleep Quality Index (PSQI) scale. RESULTS A total of 54 percent of participants reported napping with mean nap duration of 55 minutes, (SD 41.2 minutes). Compared to non-nappers, nappers were more often men (37.3% vs. 23.8%, P = .003), African American (20.4% vs.14.4%, P = .06), or diabetic (28% vs. 14.3%, P = .007). Nappers and non-nappers had similar nighttime sleep duration and quality, but nappers spent about 10 percent of their 24-hour sleep occupied in napping. In a multivariate model, the odds of napping were higher for diabetics (OR: 1.9; 95% CI: 1.2–3.0) and men (OR: 1.9; 95% CI: 1.2–3.0)). In nappers, diabetes mellitus (β = 12.3 minutes, P =.005), male gender (β = 9.0 minutes, P = .04), higher BMI (β = 0.8 minutes, P = .02), and lower MMSE (β = 2.2, P = .03) were independently associated with longer nap duration. CONCLUSION Napping was a common practice in community-dwelling older adults and did not detract from nighttime sleep duration or quality. Given its high prevalence and association with diabetes, napping behavior should be assessed as part of sleep behavior, both in future research and in clinical practice. PMID:18662202

Self-reported napping and duration and quality of sleep in the lifestyle interventions and independence for elders pilot study.

PubMed

Picarsic, Jennifer L; Glynn, Nancy W; Taylor, Christopher A; Katula, Jeffrey A; Goldman, Suzanne E; Studenski, Stephanie A; Newman, Anne B

2008-09-01

To determine the prevalence of self-reported napping and its association with subjective nighttime sleep duration and quality, as measured according to sleep-onset latency and sleep efficiency. Cross-sectional study. Lifestyle Interventions and Independence for Elders Pilot Study. Community-dwelling older adults (N=414) aged 70 to 89. Self-report questionnaire on napping and sleep derived from the Pittsburgh Sleep Quality Index (PSQI) scale. Fifty-four percent of participants reported napping, with mean nap duration of 55.0+/-41.2 minutes. Nappers were more likely to be male (37.3% vs 23.8%, P=.003) and African American (20.4% vs 14.4%, P=.06) and to have diabetes mellitus (28% vs 14.3%, P=.007) than non-nappers. Nappers and non-nappers had similar nighttime sleep duration and quality, but nappers spent approximately 10% of their 24-hour sleep occupied in napping. In a multivariate model, the odds of napping were higher for subjects with diabetes mellitus (odds ratio (OR)=1.9, 95% confidence interval (CI)=1.2-3.0) and men (OR=1.9, 95% CI=1.2-3.0). In nappers, diabetes mellitus (beta=12.3 minutes, P=.005), male sex (beta=9.0 minutes, P=.04), higher body mass index (beta=0.8 minutes, P=.02), and lower Mini-Mental State Examination score (beta=2.2 minutes, P=.03) were independently associated with longer nap duration. Napping was a common practice in community-dwelling older adults and did not detract from nighttime sleep duration or quality. Given its high prevalence and association with diabetes mellitus, napping behavior should be assessed as part of sleep behavior in future research and in clinical practice.

Napping during night shift: practices, preferences, and perceptions of critical care and emergency department nurses.

PubMed

Fallis, Wendy M; McMillan, Diana E; Edwards, Marie P

2011-04-01

Nurses working night shifts are at risk for sleep deprivation, which threatens patient and nurse safety. Little nursing research has addressed napping, an effective strategy to improve performance, reduce fatigue, and increase vigilance. To explore nurses' perceptions, experiences, barriers, and safety issues related to napping/not napping during night shift. A convenience sample of critical care nurses working night shift were interviewed to explore demographics, work schedule and environment, and napping/ not napping experiences, perceptions, and barriers. Transcripts were constantly compared, and categories and themes were identified. Participants were 13 critical care nurses with an average of 17 years' experience. Ten nurses napped regularly; 2 avoided napping because of sleep inertia. The need for and benefits of napping or not during night shift break were linked to patient and nurse safety. Ability to nap was affected by the demands of patient care and safety, staffing needs, and organizational and environmental factors. Nurses identified personal health, safety, and patient care issues supporting the need for a restorative nap during night shift. Barriers to napping exist within the organization/work environment.

Relationship between napping during night shift work and household obligations of female nursing personnel.

PubMed

Silva-Costa, Aline; Fischer, Frida Marina; Griep, Rosane Harter; Rotenberg, Lúcia

2013-01-01

Night shift employment involves displacing sleep to the daytime. For female workers, the opportunity for daytime sleep is influenced by routine housework demands, which aggravates sleep deprivation. Allowing naps to be taken during the night shift of work is a frequent practice at some hospitals and can help reduce the effects of sleep deprivation. We hypothesize that an association between domestic work and the length of naps during night work exists for nursing professionals. To test this hypothesis, two cross-sectional studies were conducted in two different hospitals. In Study 1, female workers answered questionnaires regarding sleeping habits, professional work, and housework demands. In Study 2, data regarding napping during shifts was obtained by actigraphy, a noninvasive method of monitoring the human sleep-wake cycle. The demand for the performance of housework was measured by (i) domestic work hours (total time spent performing domestic work per week), and (ii) domestic workload, which considers the degree of sharing domestic tasks and the number of people living at home. The populations from the two studies were subdivided into groups, based on the duration of napping at work. Data on naps were analyzed according to domestic demands, using the Mann-Whitney and Chi-squared tests. Among the two study populations (Studies 1 and 2), those in Study 2 were older, had shorter professional weekly work hours, worked more night shifts, and dedicated more time to housework. significant associations were only found in Study 2, where greater time napping at work was associated with both greater time spent doing housework and greater domestic workload. The known benefits of napping during night shifts seem to be especially relevant for female workers who are more sleep-deprived from working more night shifts and who have higher demands for housework.

Work schedule and self-reported hypertension - the potential beneficial role of on-shift naps for night workers.

PubMed

Rotenberg, Lúcia; Silva-Costa, Aline; Vasconcellos-Silva, Paulo Roberto; Griep, Rosane Härter

2016-01-01

Data on the association between shift work and hypertension are controversial. Sleep restriction is hypothesized to be involved in this relationship. Since on-shift nap can partly compensate for sleep deprivation among night workers, this investigation is aimed at (i) comparing the prevalence of hypertension among workers considering both current and former night work, (ii) testing the association between on-shift naps and hypertension among night workers, and (iii) analyzing the influence of sleep complaints in the association between on-shift nap and hypertension. Nap was defined as a sleep episode with duration shorter than the average nighttime sleep. A cross-sectional study was performed at the 18 largest public hospitals in Rio de Janeiro, Brazil, in 2010-2011 (N = 2588 female registered nurses). Nurses were informally allowed to nap for up to three consecutive hours during working nights. Workers completed a multidimensional questionnaire including self-reported information on physician diagnosis of hypertension, napping, and sleep complaints (insomnia, diurnal sleepiness, and non-satisfactory sleep). Epidemiological and statistical treatment of data included binomial logistic regression and interaction tests. Higher chances of hypertension were observed for both current and former night workers compared with workers with no previous experience in night work, i.e. exclusive day workers (OR = 1.68; CI95% 1.22-2.33 and OR = 1.40; CI95% 1.01-1.96, respectively) after adjustment for age, race/ethnicity, physical activity, smoking, alcohol consumption, insomnia, weekly work hours, and BMI. Compared with exclusive day workers, both non-nappers and nappers were at a higher likelihood of reporting hypertension (OR = 1.93 CI95% 1.35-2.79 and OR = 1.41 CI95% 1.08-2.20, respectively). An interaction was observed between napping behavior and insomnia (p = 0.037). In the whole sample of night workers, the lower OR for nappers was confirmed when they were directly

HDA1 and HDA3 are components of a yeast histone deacetylase (HDA) complex.

PubMed

Carmen, A A; Rundlett, S E; Grunstein, M

1996-06-28

Histone acetylation is maintained through the action of histone acetyltransferases and deacetylases and has been correlated with increased gene activity. To investigate the functional role of these enzymes in the regulation of transcription, we have purified from Saccharomyces cerevisiae two histone deacetylase activities, HDA and HDB, with molecular masses of approximately 350 and 600 kDa, respectively. In vitro, the HDA activity deacetylates all four core histones, has a preference for histone H3, and is strongly inhibited by trichostatin A (a specific inhibitor of histone deacetylases). HDB is considerably less sensitive to trichostatin A. We report the extensive purification of the HDA activity and the identification of peptides (p75, p73, p72, and p71) whose presence correlates with deacetylase activity on native polyacrylamide gels. An antibody to p75 immunoprecipitates peptides with molecular masses similar to those in the 350-kDa complex. Additionally, antibodies to p75 and p71 specifically precipitate histone deacetylase activity and co-immunoprecipitate each other. Gene disruptions of p75 (HDA1) or p71 (HDA3) cause the loss of the 350-kDa (but not the 600-kDa) activity from our chromatography profiles. These data argue strongly that HDA1 and HDA3 are subunits of the HDA complex, which is structurally distinct from the second, HDB complex.

Toddler's self-regulation strategies in a challenge context are nap-dependent.

PubMed

Miller, Alison L; Seifer, Ronald; Crossin, Rebecca; Lebourgeois, Monique K

2015-06-01

Early childhood represents a time of developmental changes in both sleep and self-regulation, a construct reflecting the ability to control one's behaviour, attention and emotions when challenged. Links between sleep and self-regulation processes have been proposed, but experimental evidence with young children is lacking. In the current study, we tested the effects of acute sleep restriction (nap deprivation) on toddlers' self-regulation. Healthy children (n = 12; four males; aged 30-36 months (33.9 ± 1.7)) slept on a strict schedule (verified with actigraphy and sleep diaries) for 5 days before each of two afternoon assessments following a nap and a no-nap condition (~11-day protocol). Children were videotaped while attempting an unsolvable puzzle, and 10 mutually exclusive self-regulation strategies were later coded. On average, children lost ~90 min of sleep on the no-nap versus the nap day. Nap deprivation resulted in moderate-to-large effects on self-regulation strategies, with decreases in scepticism (d = 0.77; 7% change), negative self-appraisal (d = 0.92; 5% change) and increases in physical self-soothing (d = 0.68; 10% change), focus on the puzzle piece that would not fit (perseveration; d = 0.50; 9% change) and insistence on completing the unsolvable puzzle (d = 0.91; 10% change). Results suggest that sleep serves an important role in the way that toddlers respond to challenging events in their daily lives. After losing daytime sleep, toddlers were less able to engage effectively in a difficult task and reverted to less mature self-regulation strategies than when they were well rested. Over time, chronically missed sleep may impair young children's self-regulation abilities, resulting in risk for social-emotional, behavioural and school problems. © 2014 European Sleep Research Society.

Studies on nap sleep in young students. Relationships between polygraphic data and the occurrence of dreams in replacing naps.

PubMed

Islas-Marroquín, J; Delgado-Brambila, H A

1998-01-01

Afternoon nap sleep was studied in 32 young male medical students who take customary naps to replace loss in nocturnal sleep. From 16 subjects, a group called dreamers was formed, and the other 16 individuals were grouped as non-dreamers. Polygraphic recordings lasting 30 min were done at a fixed time in the afternoon, and the relationship between these data and the occurrence of dreams was investigated. We found that this replacing of nap sleep can adopt different sequences and relative durations of its phases, and can also show individual variations that have a systematic relationship with the occurrence of dreams. It was observed that dreaming was closely related to the appearance, during the first 10 minutes of the nap, of Stage I with Slow Eye Movements, interrupted by Sleep Onset REM Periods (SOREMPs) and, to a lesser degree, to phases IV and III of slow sleep. According to these findings, the existence of dreamers and non-dreamers depends upon the relationship between an internal sleep-waking rhythm, and an external rhythm imposed by the daytime resting-activity schedule on the habit of dreaming, and, to a certain extent, on the mental phenomena occurring between the generation of dreams and the moment of awakening.

Daytime napping and mortality, with a special reference to cardiovascular disease: the JACC study.

PubMed

Tanabe, Naohito; Iso, Hiroyasu; Seki, Nao; Suzuki, Hiroshi; Yatsuya, Hiroshi; Toyoshima, Hideaki; Tamakoshi, Akiko

2010-02-01

Daytime napping is associated with elevated risk of all-cause mortality in the elderly. However, the association with cardiovascular disease (CVD) risk is inconsistent. From 1988 to 1990, a total of 67 129 Japanese non-workers or daytime workers (27 755 men and 39 374 women) aged 40-79 years, without a history of stroke, heart disease or cancer, completed a lifestyle questionnaire. They were followed for mortality until the end of 2003. During the 879 244 person-year follow-up, 9643 deaths (2852 from CVD, 3643 from cancer, 2392 from other internal causes, 738 from external causes and 18 from unspecified causes) were observed. After adjustment for possible confounders, subjects with a daytime napping habit had elevated hazard ratios (HRs) for mortality from all causes [HR 1.19, 95% confidence interval (CI) 1.14-1.24, P < 0.001], CVD (HR 1.31, 95% CI 1.22-1.42, P < 0.001), non-cardiovascular/non-cancer internal diseases (HR 1.26, 95% CI 1.16-1.37, P < 0.001) and external causes (HR 1.28, 95% CI 1.10-1.50, P = 0.001), but not for cancer death (HR 1.03, 95% CI 0.96-1.10, P = 0.400). The risk of CVD mortality associated with daytime napping was diminished among overweight subjects, but pronounced in those with weight loss after age 20 years, with non-regular employment, with lower education level and with a follow-up period <5 years. Daytime napping is associated with elevated risk of CVD mortality as well as non-cardiovascular/non-cancer and external deaths. Daytime napping may elevate risk of CVD death through some biological effects but, to a larger extent, some comorbid disorders causing weight loss or associated with non-regular employment and low education level could explain this association.

Prediagnosis Sleep Duration, Napping, and Mortality Among Colorectal Cancer Survivors in a Large US Cohort

PubMed Central

Arem, Hannah; Pfeiffer, Ruth; Matthews, Charles

2017-01-01

Abstract Study Objectives: Prediagnosis lifestyle factors can influence colorectal cancer (CRC) survival. Sleep deficiency is linked to metabolic dysfunction and chronic inflammation, which may contribute to higher mortality from cardiometabolic conditions and promote tumor progression. We hypothesized that prediagnosis sleep deficiency would be associated with poor CRC survival. No previous study has examined either nighttime sleep or daytime napping in relation to survival among men and women diagnosed with CRC. Methods: We examined self-reported sleep duration and napping prior to diagnosis in relation to mortality among 4869 CRC survivors in the NIH-AARP Diet and Health Study. Vital status was ascertained by linkage to the Social Security Administration Death Master File and the National Death Index. We examined the associations of sleep and napping with mortality using traditional Cox regression (total mortality) and Compositing Risk Regression (cardiovascular disease [CVD] and CRC mortality). Models were adjusted for confounders (demographics, cancer stage, grade and treatment, smoking, physical activity, and sedentary behavior) as well as possible mediators (body mass index and health status) in separate models. Results: Compared to participants reporting 7–8 hours of sleep per day, those who reported <5 hr had a 36% higher all-cause mortality risk (Hazard Ratio (95% Confidence Interval), 1.36 (1.08–1.72)). Short sleep (<5 hr) was also associated with a 54% increase in CRC mortality (Substitution Hazard Ratio (95% Confidence Interval), 1.54 (1.11–2.14)) after adjusting for confounders and accounting for competing causes of death. Compared to no napping, napping 1 hr or more per day was associated with significantly higher total and CVD mortality but not CRC mortality. Conclusion: Prediagnosis short sleep and long napping were associated with higher mortality among CRC survivors. PMID:28329353

Prediagnosis Sleep Duration, Napping, and Mortality Among Colorectal Cancer Survivors in a Large US Cohort.

PubMed

Xiao, Qian; Arem, Hannah; Pfeiffer, Ruth; Matthews, Charles

2017-04-01

Prediagnosis lifestyle factors can influence colorectal cancer (CRC) survival. Sleep deficiency is linked to metabolic dysfunction and chronic inflammation, which may contribute to higher mortality from cardiometabolic conditions and promote tumor progression. We hypothesized that prediagnosis sleep deficiency would be associated with poor CRC survival. No previous study has examined either nighttime sleep or daytime napping in relation to survival among men and women diagnosed with CRC. We examined self-reported sleep duration and napping prior to diagnosis in relation to mortality among 4869 CRC survivors in the NIH-AARP Diet and Health Study. Vital status was ascertained by linkage to the Social Security Administration Death Master File and the National Death Index. We examined the associations of sleep and napping with mortality using traditional Cox regression (total mortality) and Compositing Risk Regression (cardiovascular disease [CVD] and CRC mortality). Models were adjusted for confounders (demographics, cancer stage, grade and treatment, smoking, physical activity, and sedentary behavior) as well as possible mediators (body mass index and health status) in separate models. Compared to participants reporting 7-8 hours of sleep per day, those who reported <5 hr had a 36% higher all-cause mortality risk (Hazard Ratio (95% Confidence Interval), 1.36 (1.08-1.72)). Short sleep (<5 hr) was also associated with a 54% increase in CRC mortality (Substitution Hazard Ratio (95% Confidence Interval), 1.54 (1.11-2.14)) after adjusting for confounders and accounting for competing causes of death. Compared to no napping, napping 1 hr or more per day was associated with significantly higher total and CVD mortality but not CRC mortality. Prediagnosis short sleep and long napping were associated with higher mortality among CRC survivors. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For

The Drosophila HEM-2/NAP1 homolog KETTE controls axonal pathfinding and cytoskeletal organization.

PubMed

Hummel, T; Leifker, K; Klämbt, C

2000-04-01

In Drosophila, the correct formation of the segmental commissures depends on neuron-glial interactions at the midline. The VUM midline neurons extend axons along which glial cells migrate in between anterior and posterior commissures. Here, we show that the gene kette is required for the normal projection of the VUM axons and subsequently disrupts glial migration. Axonal projection defects are also found for many other moto- and interneurons. In addition, kette affects the cell morphology of mesodermal and epidermal derivatives, which show an abnormal actin cytoskeleton. The KETTE protein is homologous to the transmembrane protein HEM-2/NAP1 evolutionary conserved from worms to vertebrates. In vitro analysis has shown a specific interaction of the vertebrate HEM-2/NAP1 with the SH2-SH3 adapter protein NCK and the small GTPase RAC1, which both have been implicated in regulating cytoskeleton organization and axonal growth. Hypomorphic kette mutations lead to axonal defects similar to mutations in the Drosophila NCK homolog dreadlocks. Furthermore, we show that kette and dock mutants genetically interact. NCK is thought to interact with the small G proteins RAC1 and CDC42, which play a role in axonal growth. In line with these observations, a kette phenocopy can be obtained following directed expression of mutant DCDC42 or DRAC1 in the CNS midline. In addition, the kette mutant phenotype can be partially rescued by expression of an activated DRAC1 transgene. Our data suggest an important role of the HEM-2 protein in cytoskeletal organization during axonal pathfinding.

The Drosophila HEM-2/NAP1 homolog KETTE controls axonal pathfinding and cytoskeletal organization

PubMed Central

Hummel, Thomas; Leifker, Karin; Klämbt, Christian

2000-01-01

In Drosophila, the correct formation of the segmental commissures depends on neuron–glial interactions at the midline. The VUM midline neurons extend axons along which glial cells migrate in between anterior and posterior commissures. Here, we show that the gene kette is required for the normal projection of the VUM axons and subsequently disrupts glial migration. Axonal projection defects are also found for many other moto- and interneurons. In addition, kette affects the cell morphology of mesodermal and epidermal derivatives, which show an abnormal actin cytoskeleton. The KETTE protein is homologous to the transmembrane protein HEM-2/NAP1 evolutionary conserved from worms to vertebrates. In vitro analysis has shown a specific interaction of the vertebrate HEM-2/NAP1 with the SH2–SH3 adapter protein NCK and the small GTPase RAC1, which both have been implicated in regulating cytoskeleton organization and axonal growth. Hypomorphic kette mutations lead to axonal defects similar to mutations in the Drosophila NCK homolog dreadlocks. Furthermore, we show that kette and dock mutants genetically interact. NCK is thought to interact with the small G proteins RAC1 and CDC42, which play a role in axonal growth. In line with these observations, a kette phenocopy can be obtained following directed expression of mutant DCDC42 or DRAC1 in the CNS midline. In addition, the kette mutant phenotype can be partially rescued by expression of an activated DRAC1 transgene. Our data suggest an important role of the HEM-2 protein in cytoskeletal organization during axonal pathfinding. PMID:10766742

Epigenetic regulation of the NR4A orphan nuclear receptor NOR1 by histone acetylation.

PubMed

Zhao, Yue; Nomiyama, Takashi; Findeisen, Hannes M; Qing, Hua; Aono, Jun; Jones, Karrie L; Heywood, Elizabeth B; Bruemmer, Dennis

2014-12-20

The nuclear receptor NOR1 is an immediate-early response gene implicated in the transcriptional control of proliferation. Since the expression level of NOR1 is rapidly induced through cAMP response element binding (CREB) protein-dependent promoter activation, we investigated the contribution of histone acetylation to this transient induction. We demonstrate that NOR1 transcription is induced by histone deacetylase (HDAC) inhibition and by depletion of HDAC1 and HDAC3. HDAC inhibition activated the NOR1 promoter, increased histone acetylation and augmented the recruitment of phosphorylated CREB to the promoter. Furthermore, HDAC inhibition increased Ser133 phosphorylation of CREB and augmented NOR1 protein stability. These data outline previously unrecognized mechanisms of NOR1 regulation and illustrate a key role for histone acetylation in the rapid induction of NOR1. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Napping during breaks on night shift: critical care nurse managers' perceptions.

PubMed

Edwards, Marie P; McMillan, Diana E; Fallis, Wendy M

2013-01-01

Fatigue associated with shiftwork can threaten the safety and health of nurses and the patients in their care. Napping during night shift breaks has been shown to be an effective strategy to decrease fatigue and enhance performance in a variety of work environments, but appears to have mixed support within health care. The purpose of this study was to explore critical care unit managers'perceptions of and experiences with their nursing staff's napping practices on night shift, including their perceptions of the benefits and barriers to napping/not napping in terms of patient safety and nurses'personal health and safety. A survey design was used. Forty-seven Canadian critical care unit managers who were members of the Canadian Association of Critical Care Nurses responded to the web-based survey. Data analysis involved calculation of frequencies and percentages for demographic data, use of the Friedman rank test for comparison of managers' perceptions, and content analysis for responses to open-ended questions. The findings of this study offer valuable insights into the complexities and conflicts perceived by managers with respect to napping on night shift breaks by nursing staff Staff and patient health and safety issues, work and break expectations and experiences, and strengths and deficits related to organizational napping resources and policy are considerations that will be instrumental in the development of effective napping strategies and guidelines.

The effects of napping on the risk of hypertension: a systematic review and meta-analysis.

PubMed

Cheungpasitporn, Wisit; Thongprayoon, Charat; Srivali, Narat; Vijayvargiya, Priya; Andersen, Carl A; Kittanamongkolchai, Wonngarm; Sathick, Insara J Jaffer; Caples, Sean M; Erickson, Stephen B

2016-11-01

The risk of hypertension in adults who regularly take a nap is controversial. The objective of this meta-analysis was to assess the associations between napping and hypertension. A literature search was performed using MEDLINE, EMbase and The Cochrane Database of Systematic Reviews from inception through October, 2015. Studies that reported relative risks, odd ratios or hazard ratios comparing the risk of hypertension in individuals who regularly take nap were included. Pooled risk ratios (RR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. Nine observational studies with 112,267 individuals were included in the analysis to assess the risk of hypertension in nappers. The pooled RR of hypertension in nappers was 1.13 with 95% CI (0.98 to 1.30). When meta-analysis was limited only to studies assessing the risk of hypertension in daytime nappers, the pooled RR of hypertension was 1.19 with 95% CI (1.06 to 1.35). The data on association between nighttime napping in individuals who work night shift and hypertension were limited, only one observational study reported reduced risk of hypertension in nighttime nappers with odds ratio of 0.79 with 95% CI (0.63 to 1.00). Our meta-analysis demonstrates a significant association between daytime napping and hypertension. Future study is needed to assess the potential benefits of HTN screening for daytime nappers. © 2016 Chinese Cochrane Center, West China Hospital of Sichuan University and John Wiley & Sons Australia, Ltd.

Histone H1 chaperone activity of TAF-I is regulated by its subtype-dependent intramolecular interaction.

PubMed

Kajitani, Kaori; Kato, Kohsuke; Nagata, Kyosuke

2017-04-01

Linker histone H1 is involved in the regulation of gene activity through the maintenance of higher-order chromatin structure. Previously, we have shown that template activating factor-I (TAF-I or protein SET) is involved in linker histone H1 dynamics as a histone H1 chaperone. In human and murine cells, two TAF-I subtypes exist, namely TAF-Iα and TAF-Iβ. TAF-I has a highly acidic amino acid cluster in its C-terminal region and forms homo- or heterodimers through its dimerization domain. Both dimer formation and the C-terminal region of TAF-I are essential for the histone chaperone activity. TAF-Iα exhibits less histone chaperone activity compared with TAF-Iβ even though TAF-Iα and β differ only in their N-terminal regions. However, it is unclear how subtype-specific TAF-I activities are regulated. Here, we have shown that the N-terminal region of TAF-Iα autoinhibits its histone chaperone activity via intramolecular interaction with its C-terminal region. When the interaction between the N- and C-terminal regions of TAF-Iα is disrupted, TAF-Iα shows a histone chaperone activity similar to that of TAF-Iβ. Taken together, these results provide mechanistic insights into the concept that fine tuning of TAF-I histone H1 chaperone activity relies on the subtype compositions of the TAF-I dimer. © 2017 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

Daytime napping and mortality from all causes, cardiovascular disease, and cancer: a meta-analysis of prospective cohort studies.

PubMed

Zhong, Guochao; Wang, Yi; Tao, TieHong; Ying, Jun; Zhao, Yong

2015-07-01

The association between daytime napping and mortality remains controversial. We conducted a meta-analysis to examine the associations between daytime napping and the risks of death from all causes, cardiovascular disease (CVD), and cancer. PubMed and Embase databases were searched through 19 September 2014. Prospective cohort studies that provided risk estimates of daytime napping and mortality were eligible for our meta-analysis. Two investigators independently performed study screening and data extraction. A random-effects model was used to estimate the combined effect size. Subgroup analyses were conducted to identify potential effect modifiers. Twelve studies, involving 130,068 subjects, 49,791 nappers, and 19,059 deaths, were included. Our meta-analysis showed that daytime napping was associated with an increased risk of death from all causes [n = 9 studies; hazard ratio (HR), 1.22; 95% confidence interval (CI), 1.14-1.31; I(2) = 42.5%]. No significant associations between daytime napping and the risks of death from CVD (n = 6 studies; HR, 1.20; 95% CI, 0.96-1.50; I(2) = 75.0%) and cancer (n = 4 studies; HR, 1.07; 95% CI, 0.99-1.15; I(2) = 8.9%) were found. There were no significant differences in risks of all-cause and CVD mortality between subgroups stratified by the prevalence of napping, follow-up duration, outcome assessment, age, and sex. Daytime napping is a predictor of increased all-cause mortality but not of CVD and cancer mortality. However, our findings should be treated with caution because of limited numbers of included studies and potential biases. Copyright © 2015. Published by Elsevier B.V.

Micronucleus-specific histone H1 is required for micronuclear chromosome integrity in Tetrahymena thermophila

PubMed Central

Qiao, Juxia; Xu, Jing; Bo, Tao

2017-01-01

Histone H1 molecules play a key role in establishing and maintaining higher order chromatin structures. They can bind to linker DNA entering and exiting the nucleosome and regulate transcriptional activity. Tetrahymena thermophila has two histone H1, namely, macronuclear histone H1 and micronuclear histone H1 (Mlh1). Mlh1 is specifically localized at micronuclei during growth and starvation stages. Moreover, Mlh1 is localized around micronuclei and forms a specific structure during the conjugation stage. It co-localizes partially with spindle apparatus during micronuclear meiosis. Analysis of MLH1 knock-out revealed that Mlh1 was required for the micronuclear integrity and development during conjugation stage. Overexpression of Mlh1 led to abnormal conjugation progression. RT-PCR analysis indicated that the expression level of HMGB3 increased in ΔMLH1 strains, while the expression level of MLH1 increased in ΔHMGB3 cells during conjugation. These results indicate that micronuclear integrity and sexual development require normal expression level of Mlh1 and that HmgB3 and Mlh1 may functionally compensate each other in regulating micronuclear structure in T. thermophila. PMID:29095884

Histone and ribosomal RNA repetitive gene clusters of the boll weevil are linked in a tandem array.

PubMed

Roehrdanz, R; Heilmann, L; Senechal, P; Sears, S; Evenson, P

2010-08-01

Histones are the major protein component of chromatin structure. The histone family is made up of a quintet of proteins, four core histones (H2A, H2B, H3 & H4) and the linker histones (H1). Spacers are found between the coding regions. Among insects this quintet of genes is usually clustered and the clusters are tandemly repeated. Ribosomal DNA contains a cluster of the rRNA sequences 18S, 5.8S and 28S. The rRNA genes are separated by the spacers ITS1, ITS2 and IGS. This cluster is also tandemly repeated. We found that the ribosomal RNA repeat unit of at least two species of Anthonomine weevils, Anthonomus grandis and Anthonomus texanus (Coleoptera: Curculionidae), is interspersed with a block containing the histone gene quintet. The histone genes are situated between the rRNA 18S and 28S genes in what is known as the intergenic spacer region (IGS). The complete reiterated Anthonomus grandis histone-ribosomal sequence is 16,248 bp.

The impact of short night-time naps on performance, sleepiness and mood during a simulated night shift.

PubMed

Centofanti, Stephanie A; Hilditch, Cassie J; Dorrian, Jillian; Banks, Siobhan

2016-01-01

Short naps on night shift are recommended in some industries. There is a paucity of evidence to verify the sustained recovery benefits of short naps in the last few hours of the night shift. Therefore, the current study aimed to investigate the sustained recovery benefits of 30 and 10-min nap opportunities during a simulated night shift. Thirty-one healthy participants (18F, 21-35 y) completed a 3-day, between-groups laboratory study with one baseline night (22:00-07:00 h time in bed), followed by one night awake (time awake from 07:00 h on day two through 10:00 h day three) with random allocation to: a 10-min nap opportunity ending at 04:00 h, a 30-min nap opportunity ending at 04:00 h or no nap (control). A neurobehavioral test bout was administered approximately every 2 h during wake periods. There were no significant differences between nap conditions for post-nap psychomotor vigilance performance after controlling for pre-nap scores (p > 0.05). The 30-min nap significantly improved subjective sleepiness compared to the 10-min nap and no-nap control (p < 0.05). The 10-min nap significantly worsened negative mood compared to the 30-min nap and no-nap control (p < 0.01). Contrary to some evidence suggesting "power naps" can help to alleviate performance decrements, a 30-min nap opportunity at approximately 04:00 h was found to improve subjective, but not objective sleepiness. A 10-min nap may lead to increased negative mood in the hours following the nap due to a "short nap aversion" effect.

The C. elegans histone deacetylase HDA-1 is required for cell migration and axon pathfinding.

PubMed

Zinovyeva, Anna Y; Graham, Serena M; Cloud, Veronica J; Forrester, Wayne C

2006-01-01

Histone proteins play integral roles in chromatin structure and function. Histones are subject to several types of posttranslational modifications, including acetylation, which can produce transcriptional activation. The converse, histone deacetylation, is mediated by histone deacetylases (HDACs) and often is associated with transcriptional silencing. We identified a new mutation, cw2, in the Caenorhabditis elegans hda-1 gene, which encodes a histone deacetylase. Previous studies showed that a mutation in hda-1, e1795, or reduction of hda-1 RNA by RNAi causes defective vulval and gonadal development leading to sterility. The hda-1(cw2) mutation causes defective vulval development and reduced fertility, like hda-1(e1795), albeit with reduced severity. Unlike the previously reported hda-1 mutation, hda-1(cw2) mutants are viable as homozygotes, although many die as embryos or larvae, and are severely uncoordinated. Strikingly, in hda-1(cw2) mutants, axon pathfinding is defective; specific axons often appear to wander randomly or migrate in the wrong direction. In addition, the long range migrations of three neuron types and fasciculation of the ventral nerve cord are defective. Together, our studies define a new role for HDA-1 in nervous system development, and provide the first evidence for HDAC function in regulating neuronal axon guidance.

Improved Therapeutic Effect against Leukemia by a Combination of the Histone Methyltransferase Inhibitor Chaetocin and the Histone Deacetylase Inhibitor Trichostatin A

PubMed Central

Tran, Huong Thi Thanh; Kim, Hee Nam; Lee, Il-Kwon; Nguyen-Pham, Thanh-Nhan; Ahn, Jae-Sook; Kim, Yeo-Kyeoung; Lee, Je-Jung; Park, Kyeong-Soo; Kook, Hoon

2013-01-01

SUV39H1 is a histone 3 lysine 9 (H3K9)-specific methyltransferase that is important for heterochromatin formation and the regulation of gene expression. Chaetocin specifically inhibits SUV39H1, resulted in H3K9 methylation reduction as well as reactivation of silenced genes in cancer cells. Histone deacetylase (HDAC) inhibitors inhibit deacetylases and accumulate high levels of acetylation lead to cell cycle arrest and apoptosis. In this study, we demonstrated that treatment with chaetocin enhanced apoptosis in human leukemia HL60, KG1, Kasumi, K562, and THP1 cells. In addition, chaetocin induced the expression of cyclin-dependent kinase inhibitor 2B (p15), E-cadherin (CDH1) and frizzled family receptor 9 (FZD9) through depletion of SUV39H1 and reduced H3K9 methylation in their promoters. Co-treatment with chaetocin and HDAC inhibitor trichostatin A (TSA) dramatically increased apoptosis and produced greater activation of genes. Furthermore, this combined treatment significantly increased loss of SUV39H1 and reduced histone H3K9 trimethylation responses accompanied by increased acetylation. Importantly, co-treatment with chaetocin and TSA produced potent antileukemic effects in leukemia cells derived from patients. These in vitro findings suggest that combination therapy with SUV39H1 and HDAC inhibitors may be of potential value in the treatment of leukemia. PMID:23400519

Explorative study on isoform-selective histone deacetylase inhibitors.

PubMed

Suzuki, Takayoshi

2009-09-01

Histone deacetylases (HDACs) catalyze the deacetylation of the acetylated lysine residues of histones and non-histone proteins, and are involved in various fundamental life phenomena, such as gene expression and cell cycle progression. Thus far, eighteen HDAC family members (HDAC1-11 and SIRT1-7) have been identified, but the functions of the HDAC isoforms are not yet fully understood. In addition, some of the HDAC isoforms have been suggested to be associated with various disease states, including cancer and neurodegenerative disorders. Therefore, isoform-selective HDAC inhibitors are of great interest, not only as tools for probing the biological functions of the isoforms, but also as candidate therapeutic agents with few side effects. It was against this background that we initiated research programs to identify isoform-selective HDAC inhibitors. We designed HDAC inhibitors based on the three-dimensional structure of the enzyme and on the proposed catalytic mechanism of HDACs, and found several isoform-selective HDAC inhibitors. Furthermore, we elucidated the functions of HDAC6 by chemical genetic approaches using these inhibitors. The results of this research also suggested the feasibility of using isoform-selective HDAC inhibitors as therapeutic agents.

Arabidopsis Histone Reader EMSY-LIKE 1 Binds H3K36 and Suppresses Geminivirus Infection.

PubMed

Coursey, Tami; Milutinovic, Milica; Regedanz, Elizabeth; Brkljacic, Jelena; Bisaro, David M

2018-06-06

Histone post-translational modifications (PTMs) impart information that regulates chromatin structure and activity. Their effects are mediated by histone reader proteins that bind specific PTMs to modify chromatin and/or recruit appropriate effectors to alter the chromatin landscape. Despite their crucial juxtaposition between information and functional outcome, relatively few plant histone readers have been identified, and nothing is known about their impact on viral chromatin and pathogenesis. We used the geminivirus Cabbage leaf curl virus (CaLCuV) as a model to functionally characterize two recently identified reader proteins, EMSY-LIKE 1 and 3 (EML1 and EML3), which contain Tudor-like Agenet domains predictive of histone PTM binding function. Here, we show that mutant Arabidopsis plants exhibit contrasting hypersusceptible ( eml1 ) and tolerant ( eml3 ) responses to CaLCuV infection, and that EML1 deficiency correlates with RNA polymerase II (Pol II) enrichment on viral chromatin and upregulated viral gene expression. Consistent with reader activity, EML1 and EML3 associate with nucleosomes and with CaLCuV chromatin, suggesting a direct impact on pathogenesis. We also demonstrate that EML1 and EML3 bind peptides containing histone H3 lysine 36 (H3K36), a PTM usually associated with active gene expression. The interaction encompasses multiple H3K36 PTMs, including methylation and acetylation, suggesting nuanced regulation. Further, EML1 and EML3 associate with similar regions of viral chromatin, implying possible competition between the two readers. Regions of EML1 and EML3 association correlate with sites of trimethylated H3K36 (H3K36me3) enrichment, consistent with regulation of geminivirus chromatin by direct EML targeting. IMPORTANCE Histone PTMs convey information that regulates chromatin compaction and DNA accessibility. Histone reader proteins bind specific PTMs and translate their effects by modifying chromatin and/or by recruiting effectors that alter

Age- and gender-specific associations of napping duration with type 2 diabetes mellitus in a Chinese rural population: the RuralDiab study.

PubMed

Liu, Ruihua; Li, Yuqian; Wang, Fang; Liu, Xiaotian; Zhou, Hao; Wang, Panpan; Fan, Jingjing; Xu, Fei; Yang, Kaili; Hu, Dongsheng; Bie, Ronghai; Wang, Chongjian

2017-05-01

The consistency and strength of the relationship between napping duration and type 2 diabetes mellitus (T2DM) remained uncertain, especially in the rural population. The purpose of this study was to explore the relationship between napping duration and T2DM in a Chinese rural population. A total of 12663 participants (4365 males and 8298 females) were derived from the RuralDiab study in China. Napping duration was obtained through a standardized questionnaire, and was divided into five categories: no napping (reference), 1∼, 31∼, 61∼, and ≥91 min. Fasting blood glucose was measured. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). A meta-analysis including seven studies was conducted to validate the result of the RuralDiab study. The crude and age-standardized prevalence of T2DM were 10.31% and 8.14%, respectively. Compared with no napping, the adjusted OR (95%CI) for napping duration ≥91 min was 1.23 (1.05-1.45). A similar relationship was found only in females aged 45-54 years, but not in males and other age group females. In addition, napping duration was associated with T2DM in a positive dose-dependent manner among females aged 45-54 years (P for trend <0.05). The meta-analysis demonstrated this association, and the pooled OR (95%CI) for the longest napping duration compared with no napping was 1.28 (1.22-1.35). Longer napping duration is associated with higher risk of T2DM in the Chinese rural population, and this association varies across gender and age. Further multi-center prospective researches are needed to confirm the relationship and reveal underlying mechanisms. Copyright © 2016 Elsevier B.V. All rights reserved.

The histone shuffle: histone chaperones in an energetic dance

PubMed Central

Das, Chandrima; Tyler, Jessica K.; Churchill, Mair E.A.

2014-01-01

Our genetic information is tightly packaged into a rather ingenious nucleoprotein complex called chromatin in a manner that enables it to be rapidly accessed during genomic processes. Formation of the nucleosome, which is the fundamental unit of chromatin, occurs via a stepwise process that is reversed to enable the disassembly of nucleosomes. Histone chaperone proteins have prominent roles in facilitating these processes as well as in replacing old histones with new canonical histones or histone variants during the process of histone exchange. Recent structural, biophysical and biochemical studies have begun to shed light on the molecular mechanisms whereby histone chaperones promote chromatin assembly, disassembly and histone exchange to facilitate DNA replication, repair and transcription. PMID:20444609

Structural insights into the histone H1-nucleosome complex

PubMed Central

Zhou, Bing-Rui; Feng, Hanqiao; Kato, Hidenori; Dai, Liang; Yang, Yuedong; Zhou, Yaoqi; Bai, Yawen

2013-01-01

Linker H1 histones facilitate formation of higher-order chromatin structures and play important roles in various cell functions. Despite several decades of effort, the structural basis of how H1 interacts with the nucleosome remains elusive. Here, we investigated Drosophila H1 in complex with the nucleosome, using solution nuclear magnetic resonance spectroscopy and other biophysical methods. We found that the globular domain of H1 bridges the nucleosome core and one 10-base pair linker DNA asymmetrically, with its α3 helix facing the nucleosomal DNA near the dyad axis. Two short regions in the C-terminal tail of H1 and the C-terminal tail of one of the two H2A histones are also involved in the formation of the H1–nucleosome complex. Our results lead to a residue-specific structural model for the globular domain of the Drosophila H1 in complex with the nucleosome, which is different from all previous experiment-based models and has implications for chromatin dynamics in vivo. PMID:24218562

The Linker Histone GH1-HMGA1 Is Involved in Telomere Stability and DNA Damage Repair1[OPEN

PubMed Central

Charbonnel, Cyril; Benyahya, Fatiha; Butter, Falk

2018-01-01

Despite intensive searches, few proteins involved in telomere homeostasis have been identified in plants. Here, we used pull-down assays to identify potential telomeric interactors in the model plant species Arabidopsis (Arabidopsis thaliana). We identified the candidate protein GH1-HMGA1 (also known as HON4), an uncharacterized linker histone protein of the High Mobility Group Protein A (HMGA) family in plants. HMGAs are architectural transcription factors and have been suggested to function in DNA damage repair, but their precise biological roles remain unclear. Here, we show that GH1-HMGA1 is required for efficient DNA damage repair and telomere integrity in Arabidopsis. GH1-HMGA1 mutants exhibit developmental and growth defects, accompanied by ploidy defects, increased telomere dysfunction-induced foci, mitotic anaphase bridges, and degraded telomeres. Furthermore, mutants have a higher sensitivity to genotoxic agents such as mitomycin C and γ-irradiation. Our work also suggests that GH1-HMGA1 is involved directly in the repair process by allowing the completion of homologous recombination. PMID:29622687

Napping reverses the salivary interleukin-6 and urinary norepinephrine changes induced by sleep restriction.

PubMed

Faraut, Brice; Nakib, Samir; Drogou, Catherine; Elbaz, Maxime; Sauvet, Fabien; De Bandt, Jean-Pascal; Léger, Damien

2015-03-01

Neuroendocrine and immune stresses imposed by chronic sleep restriction are known to be involved in the harmful cardiovascular effects associated with poor sleep. Despite a well-known beneficial effect of napping on alertness, its effects on neuroendocrine stress and immune responses after sleep restriction are largely unknown. This study was a strictly controlled (sleep-wake status, light environment, caloric intake), crossover, randomized design in continuously polysomnography-monitored subjects. The study was conducted in a laboratory-based study. The subjects were 11 healthy young men. We investigated the effects on neuroendocrine and immune biomarkers of a night of sleep restricted to 2 h followed by a day without naps or with 30 minute morning and afternoon naps, both conditions followed by an ad libitum recovery night starting at 20:00. Salivary interleukin-6 and urinary catecholamines were assessed throughout the daytime study periods. The increase in norepinephrine values seen at the end of the afternoon after the sleep-restricted night was not present when the subjects had the opportunity to take naps. Interleukin-6 changes observed after sleep deprivation were also normalized after napping. During the recovery day in the no-nap condition, there were increased levels of afternoon epinephrine and dopamine, which was not the case in the nap condition. A recovery night after napping was associated with a reduced amount of slow-wave sleep compared to after the no-nap condition. Our data suggest that napping has stress-releasing and immune effects. Napping could be easily applied in real settings as a countermeasure to the detrimental health consequences of sleep debt.

The Concept of Qailulah (Midday Napping) from Neuroscientific and Islamic Perspectives.

PubMed

Tumiran, Mohd Amzari; Rahman, Noor Naemah Abdul; Saat, Rohaida Mohd; Kabir, Nurul; Zulkifli, Mohd Yakub; Adli, Durriyyah Sharifah Hasan

2015-08-13

Napping/siesta during the day is a phenomenon, which is widely practised in the world. However, the timing, frequency, and duration may vary. The basis of napping is also diverse, but it is mainly done for improvement in alertness and general well-being. Neuroscience reveals that midday napping improves memory, enhances alertness, boosts wakefulness and performance, and recovers certain qualities of lost night sleep. Interestingly, Islam, the religion of the Muslims, advocates midday napping primarily because it was a practice preferred by Prophet Muhammad (pbuh). The objectives of this review were to investigate and compare identical key points on focused topic from both neuroscientific and Islamic perspectives and make recommendations for future researches.

Endometriosis Is Characterized by a Distinct Pattern of Histone 3 and Histone 4 Lysine Modifications

PubMed Central

Monteiro, Janice B.; Colón-Díaz, Maricarmen; García, Miosotis; Gutierrez, Sylvia; Colón, Mariano; Seto, Edward; Laboy, Joaquín

2014-01-01

Background: The histone modification patterns in endometriosis have not been fully characterized. This gap in knowledge results in a poor understanding of the epigenetic mechanisms (and potential therapeutic targets) at play. We aimed to (1) assess global acetylation status of histone 3 (H3) and histone 4 (H4), (2) measure levels of H3 and H4 lysine (K) acetylation and methylation, and (3) to identify histone acetylation patterns in promoter regions of candidate genes in tissues from patients and controls. Methods: Global and K-specific acetylation/methylation levels of histones were measured in 24 lesions, 15 endometrium from patients, and 26 endometrium from controls. Chromatin immunoprecipitation (ChIP)–polymerase chain reaction was used to determine the histone acetylation status of the promoter regions of candidate genes in tissues. Results: The lesions were globally hypoacetylated at H3 (but not H4) compared to eutopic endometrium from controls. Lesions had significantly lower levels of H3K9ac and H4K16ac compared to eutopic endometrium from patients and controls. Tissues from patients were hypermethylated at H3K4, H3K9, and H3K27 compared to endometrium from controls. The ChIP analysis showed hypoacetylation of H3/H4 within promoter regions of candidate genes known to be downregulated in endometriosis (e.g., HOXA10, ESR1, CDH1, and p21WAF1/Cip1) in lesions versus control endometrium. The stereoidogenic factor 1 (SF1) promoter region was enriched for acetylated H3 and H4 in lesions versus control tissues, correlating with its reported high expression in lesions. Conclusions: This study describes the histone code of lesions and endometrium from patients with endometriosis and provides support for a possible role of histone modification in modulation of gene expression in endometriosis. PMID:23899551

Histone deacetylase 1 is required for the development of the zebrafish inner ear

PubMed Central

He, Yingzi; Tang, Dongmei; Li, Wenyan; Chai, Renjie; Li, Huawei

2016-01-01

Histone deacetylase 1 (HDAC1) has been reported to be important for multiple aspects of normal embryonic development, but little is known about its function in the development of mechanosensory organs. Here, we first confirmed that HDAC1 is expressed in the developing otic vesicles of zebrafish by whole-mount in situ hybridization. Knockdown of HDAC1 using antisense morpholino oligonucleotides in zebrafish embryos induced smaller otic vesicles, abnormal otoliths, malformed or absent semicircular canals, and fewer sensory hair cells. HDAC1 loss of function also caused attenuated expression of a subset of key genes required for otic vesicle formation during development. Morpholino-mediated knockdown of HDAC1 resulted in decreased expression of members of the Fgf family in the otic vesicles, suggesting that HDAC1 is involved in the development of the inner ear through regulation of Fgf signaling pathways. Taken together, our results indicate that HDAC1 plays an important role in otic vesicle formation. PMID:26832938

LSD1 knockdown reveals novel histone lysine methylation in human breast cancer MCF-7 cells.

PubMed

Jin, Yue; Huo, Bo; Fu, Xueqi; Cheng, Zhongyi; Zhu, Jun; Zhang, Yu; Hao, Tian; Hu, Xin

2017-08-01

Histone lysine methylation, which plays an important role in the regulation of gene expression, genome stability, chromosome conformation and cell differentiation, is a dynamic process that is collaboratively regulated by lysine methyltransferases (KMTs) and lysine demethylases (KDMs). LSD1, the first identified KDMs, catalyzes the demethylation of mono- and di-methylated H3K4 and H3K9. Here, we systematically investigated the effects of LSD1 knockdown on histone methylations. Surprisingly, in addition to H3K4 and H3K9, the methylation level on other histone lysines, such as H3K27, H3K36 and H3K79, are also increased. The expression of SOX2, E-cadherin and FoxA2 are increased upon LSD1 knockdown, and the methylation level of H3K4, H3K27 and H3K36 in the promoter region of these genes are all changed after LSD1 knockdown. Our results show that LSD1 knockdown has a broad effect on histone lysine methylation, which indicates that LSD1 regulates histone lysine methylation in collaboration with other KMTs and KDMs. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Neuroprotective effects of NAP against excitotoxic brain damage in the newborn mice: implications for cerebral palsy.

PubMed

Sokolowska, P; Passemard, S; Mok, A; Schwendimann, L; Gozes, I; Gressens, P

2011-01-26

Activity-dependent neuroprotective protein (ADNP) was shown to be essential for embryogenesis and brain development while NAP, an active motif of ADNP, is neuroprotective in a broad range of neurodegenerative disorders. In the present study, we examined the protective potential of ADNP/NAP in a mouse model of excitotoxic brain lesion mimicking brain damage associated with cerebral palsy. We demonstrated that NAP had a potent neuroprotective effect against ibotenate-induced excitotoxic damage in the cortical plate and the white matter of P5 mice, and moderate against brain lesions of P0 mice. In contrast, endogenous ADNP appears not to be involved in the response to excitotoxic challenge in the studied model. Our findings further show that NAP reduced the number of apoptotic neurons through activation of PI-3K/Akt pathway in the cortical plate or both PI-3K/Akt and MAPK/MEK1 kinases in the white matter. In addition, NAP prevented ibotenate-induced loss of pre-oligodendrocytes without affecting the number of astrocytes or activated microglia around the site of injection. These findings indicate that protective actions of NAP are mediated by triggering transduction pathways that are crucial for neuronal and oligodendroglial survival, thus, NAP might be a promising therapeutic agent for treating developing brain damage. © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

One-pot refolding of core histones from bacterial inclusion bodies allows rapid reconstitution of histone octamer.

PubMed

Lee, Young-Tae; Gibbons, Garrett; Lee, Shirley Y; Nikolovska-Coleska, Zaneta; Dou, Yali

2015-06-01

We report an optimized method to purify and reconstitute histone octamer, which utilizes high expression of histones in inclusion bodies but eliminates the time consuming steps of individual histone purification. In the newly modified protocol, Xenopus laevis H2A, H2B, H3, and H4 are expressed individually into inclusion bodies of bacteria, which are subsequently mixed together and denatured in 8M guanidine hydrochloride. Histones are refolded and reconstituted into soluble octamer by dialysis against 2M NaCl, and metal-affinity purified through an N-terminal polyhistidine-tag added on the H2A. After cleavage of the polyhistidine-tag, histone octamer is further purified by size exclusion chromatography. We show that the nucleosomes reconstituted using the purified histone octamer above are fully functional. They serve as effective substrates for the histone methyltransferases DOT1L and MLL1. Small angle X-ray scattering further confirms that the reconstituted nucleosomes have correct structural integration of histone octamer and DNA as observed in the X-ray crystal structure. Our new protocol enables rapid reconstitution of histone octamer with an optimal yield. We expect this simplified approach to facilitate research using recombinant nucleosomes in vitro. Copyright © 2015 Elsevier Inc. All rights reserved.

Toddler’s Self-Regulation Strategies in a Challenge Context are Nap-Dependent

PubMed Central

Miller, Alison L.; Seifer, Ronald; Crossin, Rebecca; LeBourgeois, Monique K.

2015-01-01

SUMMARY Early childhood represents a time of developmental changes in both sleep and self-regulation, a construct reflecting the ability to control one’s behavior, attention, and emotion when challenged. Links between sleep and self-regulation processes have been proposed, but experimental evidence with young children is lacking. In the current study, we tested the effects of acute sleep restriction (nap deprivation) on toddlers’ self-regulation. Healthy children (n=12; 4 males; 30–36 months (33.9±1.7) slept on a strict schedule (verified with actigraphy and sleep diaries) for 5 days before each of two afternoon assessments following a Nap and a No-Nap condition (~11-day protocol). Children were videotaped while attempting an unsolvable puzzle, and 10 mutually exclusive self-regulation strategies were later coded. On average, children lost ~90 min of sleep on the No-Nap versus the Nap day. Nap deprivation resulted in moderate-to-large effects on self-regulation strategies, with decreases in skepticism (d=0.77; 7% change), negative self-appraisal (d=0.92; 5% change), and increases in physical self-soothing (d=0.68; 10% change), focus on the puzzle piece that would not fit (perseveration; d=0.50; 9% change), and insistence on completing the unsolvable puzzle (d=0.91; 10% change). Results suggest sleep serves an important role in the way toddlers respond to challenging events in their daily lives. After losing daytime sleep, toddlers were less able to effectively engage in a difficult task and reverted to less mature self-regulation strategies, than when they were well-rested. Over time, chronically missed sleep may impair young children’s self-regulation abilities, resulting in risk for social-emotional, behavioral, and school problems. PMID:25394169

Comparative Modeling and Benchmarking Data Sets for Human Histone Deacetylases and Sirtuin Families

PubMed Central

Xia, Jie; Tilahun, Ermias Lemma; Kebede, Eyob Hailu; Reid, Terry-Elinor; Zhang, Liangren; Wang, Xiang Simon

2015-01-01

Histone Deacetylases (HDACs) are an important class of drug targets for the treatment of cancers, neurodegenerative diseases and other types of diseases. Virtual screening (VS) has become fairly effective approaches for drug discovery of novel and highly selective Histone Deacetylases Inhibitors (HDACIs). To facilitate the process, we constructed the Maximal Unbiased Benchmarking Data Sets for HDACs (MUBD-HDACs) using our recently published methods that were originally developed for building unbiased benchmarking sets for ligand-based virtual screening (LBVS). The MUBD-HDACs covers all 4 Classes including Class III (Sirtuins family) and 14 HDACs isoforms, composed of 631 inhibitors and 24,609 unbiased decoys. Its ligand sets have been validated extensively as chemically diverse, while the decoy sets were shown to be property-matching with ligands and maximal unbiased in terms of “artificial enrichment” and “analogue bias”. We also conducted comparative studies with DUD-E and DEKOIS 2.0 sets against HDAC2 and HDAC8 targets, and demonstrate that our MUBD-HDACs is unique in that it can be applied unbiasedly to both LBVS and SBVS approaches. In addition, we defined a novel metric, i.e. NLBScore, to detect the “2D bias” and “LBVS favorable” effect within the benchmarking sets. In summary, MUBD-HDACs is the only comprehensive and maximal-unbiased benchmark data sets for HDACs (including Sirtuins) that is available so far. MUBD-HDACs is freely available at http://www.xswlab.org/. PMID:25633490

Comparative modeling and benchmarking data sets for human histone deacetylases and sirtuin families.

PubMed

Xia, Jie; Tilahun, Ermias Lemma; Kebede, Eyob Hailu; Reid, Terry-Elinor; Zhang, Liangren; Wang, Xiang Simon

2015-02-23

Histone deacetylases (HDACs) are an important class of drug targets for the treatment of cancers, neurodegenerative diseases, and other types of diseases. Virtual screening (VS) has become fairly effective approaches for drug discovery of novel and highly selective histone deacetylase inhibitors (HDACIs). To facilitate the process, we constructed maximal unbiased benchmarking data sets for HDACs (MUBD-HDACs) using our recently published methods that were originally developed for building unbiased benchmarking sets for ligand-based virtual screening (LBVS). The MUBD-HDACs cover all four classes including Class III (Sirtuins family) and 14 HDAC isoforms, composed of 631 inhibitors and 24609 unbiased decoys. Its ligand sets have been validated extensively as chemically diverse, while the decoy sets were shown to be property-matching with ligands and maximal unbiased in terms of "artificial enrichment" and "analogue bias". We also conducted comparative studies with DUD-E and DEKOIS 2.0 sets against HDAC2 and HDAC8 targets and demonstrate that our MUBD-HDACs are unique in that they can be applied unbiasedly to both LBVS and SBVS approaches. In addition, we defined a novel metric, i.e. NLBScore, to detect the "2D bias" and "LBVS favorable" effect within the benchmarking sets. In summary, MUBD-HDACs are the only comprehensive and maximal-unbiased benchmark data sets for HDACs (including Sirtuins) that are available so far. MUBD-HDACs are freely available at http://www.xswlab.org/ .

The Effect of Cognitive Activity on Sleep Maintenance in a Subsequent Daytime Nap.

PubMed

Arzilli, Cinzia; Cerasuolo, Mariangela; Conte, Francesca; Bittoni, Valentina; Gatteschi, Claudia; Albinni, Benedetta; Giganti, Fiorenza; Ficca, Gianluca

2018-01-25

The aim of this study is to assess the effects of a learning task on the characteristics of a subsequent daytime nap. Thirty-eight subjects were administered a control nap (C) and one preceded by a cognitive training session (TR). Relative to C, TR naps showed significantly increased sleep duration with decreased sleep latency, as well as significantly increased sleep efficiency due to reduced awakening frequency. Meaningful trends were also found toward an increase of Stage 2 sleep proportion and a reduction of Stage 1 sleep, percentage of wake after sleep onset (WASO), and frequency of state transitions. Our results indicate that presleep learning favors sleep propensity and maintenance, offering the possibility to explore planned cognitive training as a low-cost treatment for sleep impairments.

Epigenetic Metabolite Acetate Inhibits Class I/II Histone Deacetylases, Promotes Histone Acetylation, and Increases HIV-1 Integration in CD4+ T Cells.

PubMed

Bolduc, Jean-François; Hany, Laurent; Barat, Corinne; Ouellet, Michel; Tremblay, Michel J

2017-08-15

In this study, we investigated the effect of acetate, the most concentrated short-chain fatty acid (SCFA) in the gut and bloodstream, on the susceptibility of primary human CD4 + T cells to HIV-1 infection. We report that HIV-1 replication is increased in CD3/CD28-costimulated CD4 + T cells upon acetate treatment. This enhancing effect correlates with increased expression of the early activation marker CD69 and impaired class I/II histone deacetylase (HDAC) activity. In addition, acetate enhances acetylation of histones H3 and H4 and augments HIV-1 integration into the genome of CD4 + T cells. Thus, we propose that upon antigen presentation, acetate influences class I/II HDAC activity that transforms condensed chromatin into a more relaxed structure. This event leads to a higher level of viral integration and enhanced HIV-1 production. In line with previous studies showing reactivation of latent HIV-1 by SCFAs, we provide evidence that acetate can also increase the susceptibility of primary human CD4 + T cells to productive HIV-1 infection. IMPORTANCE Alterations in the fecal microbiota and intestinal epithelial damage involved in the gastrointestinal disorder associated with HIV-1 infection result in microbial translocation that leads to disease progression and virus-related comorbidities. Indeed, notably via production of short-chain fatty acids, bacteria migrating from the lumen to the intestinal mucosa could influence HIV-1 replication by epigenetic regulatory mechanisms, such as histone acetylation. We demonstrate that acetate enhances virus production in primary human CD4 + T cells. Moreover, we report that acetate impairs class I/II histone deacetylase activity and increases integration of HIV-1 DNA into the host genome. Therefore, it can be postulated that bacterial metabolites such as acetate modulate HIV-1-mediated disease progression. Copyright © 2017 American Society for Microbiology.

Cot, a novel kinase of histone H3, induces cellular transformation through up-regulation of c-fos transcriptional activity.

PubMed

Choi, Hong Seok; Kang, Bong Seok; Shim, Jung-Hyun; Cho, Yong-Yeon; Choi, Bu Young; Bode, Ann M; Dong, Zigang

2008-01-01

Post-translational modification of histones is critical for gene expression, mitosis, cell growth, apoptosis, and cancer development. Thus, finding protein kinases that are responsible for the phosphorylation of histones at critical sites is considered an important step in understanding the process of histone modification. The serine/threonine kinase Cot is a member of the mitogen-activated protein kinase (MAPK) kinase kinase family. We show here that Cot can phosphorylate histone H3 at Ser-10 in vivo and in vitro, and that the phosphorylation of histone H3 at Ser-10 is required for Cot-induced cell transformation. We found that activated Cot is recruited to the c-fos promoter resulting in increased activator protein-1 (AP-1) transactivation. The formation of the Cot-c-fos promoter complex was also apparent when histone H3 was phosphorylated at Ser-10. Furthermore, the use of dominant negative mutants of histone H3 revealed that Cot was required for phosphorylation of histone H3 at Ser-10 to induce neoplastic cell transformation. These results revealed an important function of Cot as a newly discovered histone H3 kinase. Moreover, the transforming ability of Cot results from the coordinated activation of histone H3, which ultimately converges on the regulation of the transcriptional activity of the c-fos promoter, followed by AP-1 transactivation activity.

Association of daytime napping with prediabetes and diabetes in a Chinese population: Results from the baseline survey of the China Health and Retirement Longitudinal Study.

PubMed

Yin, Xin; Liu, Qi; Wei, Jiate; Meng, Xin; Jia, Chongqi

2018-04-01

Only a few studies have investigated the effects of daytime napping on diabetes, and these studies have reported conflicting results. The aim of the present study was to examine whether daytime napping is associated with a higher risk of prediabetes and diabetes. The present cross-sectional study of napping duration in relation to prediabetes and diabetes was conducted in 12 277 participants. Data from the first wave (2011) of the China Health and Retirement Longitudinal Study were used. Daytime napping was divided into four groups: no napping (reference) and napping for 1-30, 31-90, and >90 min. Multinomial logistic regression was used to obtain odds ratios (ORs) and 95% confidence intervals (CIs). Individuals who reported taking daily afternoon naps accounted for 53.39% of all participants. Nappers had a higher prevalence of prediabetes and diabetes than non-nappers. Compared with the reference group, the weighted fully adjusted ORs (95% CI) were 1.36 (1.10-1.68) and 1.61 (1.22-2.13) for napping >90 min in prediabetic and diabetic patients, respectively. Long daytime napping duration was positively associated with prediabetes and diabetes. Further physiological and cohort studies are needed to confirm these results and elucidate potential mechanisms. © 2017 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Silencing of IFN-stimulated gene transcription is regulated by histone H1 and its chaperone TAF-I

PubMed Central

Kadota, Shinichi; Nagata, Kyosuke

2014-01-01

Chromatin structure and its alteration play critical roles in the regulation of transcription. However, the transcriptional silencing mechanism with regard to the chromatin structure at an unstimulated state of the interferon (IFN)-stimulated gene (ISG) remains unclear. Here we investigated the role of template activating factor-I (TAF-I, also known as SET) in ISG transcription. Knockdown (KD) of TAF-I increased ISG transcript and simultaneously reduced the histone H1 level on the ISG promoters during the early stages of transcription after IFN stimulation from the unstimulated state. The transcription factor levels on the ISG promoters were increased in TAF-I KD cells only during the early stages of transcription. Furthermore, histone H1 KD also increased ISG transcript. TAF-I and histone H1 double KD did not show the additive effect in ISG transcription, suggesting that TAF-I and histone H1 may act on the same regulatory pathway to control ISG transcription. In addition, TAF-I KD and histone H1 KD affected the chromatin structure near the ISG promoters. On the basis of these findings, we propose that TAF-I and its target histone H1 are key regulators of the chromatin structure at the ISG promoter to maintain the silent state of ISG transcription. PMID:24878923

Heterogeneous Antibody-Based Activity Assay for Lysine Specific Demethylase 1 (LSD1) on a Histone Peptide Substrate.

PubMed

Schmitt, Martin L; Ladwein, Kathrin I; Carlino, Luca; Schulz-Fincke, Johannes; Willmann, Dominica; Metzger, Eric; Schilcher, Pierre; Imhof, Axel; Schüle, Roland; Sippl, Wolfgang; Jung, Manfred

2014-07-01

Posttranslational modifications of histone tails are very important for epigenetic gene regulation. The lysine-specific demethylase LSD1 (KDM1A/AOF2) demethylates in vitro predominantly mono- and dimethylated lysine 4 on histone 3 (H3K4) and is a promising target for drug discovery. We report a heterogeneous antibody-based assay, using dissociation-enhanced lanthanide fluorescent immunoassay (DELFIA) for the detection of LSD1 activity. We used a biotinylated histone 3 peptide (amino acids 1-21) with monomethylated lysine 4 (H3K4me) as the substrate for the detection of LSD1 activity with antibody-mediated quantitation of the demethylated product. We have successfully used the assay to measure the potency of reference inhibitors. The advantage of the heterogeneous format is shown with cumarin-based LSD1 inhibitor candidates that we have identified using virtual screening. They had shown good potency in an established LSD1 screening assay. The new heterogeneous assay identified them as false positives, which was verified using mass spectrometry. © 2014 Society for Laboratory Automation and Screening.

Poor sleep moderates the relationship between daytime napping and inflammation in Black and White men.

PubMed

Jakubowski, Karen P; Boylan, Jennifer M; Cundiff, Jenny M; Matthews, Karen A

2017-10-01

To test whether napping was associated with 2 inflammatory markers with known relationships to cardiovascular disease: high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6). Because IL-6 is known to impact central inflammatory processes that relate to sleep regulation, including subjective fatigue, we tested whether this relationship was moderated by sleep duration, sleep efficiency, and self-reported sleep quality. Cross-sectional. A community sample of Black and White men (N=253) completed a week of actigraphy and diary measures of sleep and napping and provided a fasting blood sample. Napping was measured as the proportion of days with at least 30 minutes napped and the average minutes napped per day. Linear regressions adjusted for race, socioeconomic status, employment, body mass index, smoking, medications that affect sleep or inflammation, working the nightshift, and day-sleeping status, followed by interaction terms between napping and sleep duration, efficiency, and quality, respectively. There were no significant main effects of actigraphy- or diary-measured napping on IL-6 or hsCRP. Moderation analyses indicated elevated IL-6 values among men who napped more days (by actigraphy) and demonstrated short sleep duration (P=.03). Moderation analyses also indicated elevated IL-6 among men who demonstrated greater average minutes napped (by actigraphy) and short sleep duration (P<.001), low efficiency (P=.03), and poor quality (P=.03). Moderation analyses involving diary napping or hsCRP were not significant. Actigraphy-assessed daytime napping is related to higher IL-6 in men who demonstrate worse sleep characteristics. Daytime napping may pose additional risk for inflammation beyond the known risk conferred by short sleep. Copyright © 2017 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.

Coordinating cell cycle-regulated histone gene expression through assembly and function of the Histone Locus Body

PubMed Central

Duronio, Robert J.; Marzluff, William F.

2017-01-01

ABSTRACT Metazoan replication-dependent (RD) histone genes encode the only known cellular mRNAs that are not polyadenylated. These mRNAs end instead in a conserved stem-loop, which is formed by an endonucleolytic cleavage of the pre-mRNA. The genes for all 5 histone proteins are clustered in all metazoans and coordinately regulated with high levels of expression during S phase. Production of histone mRNAs occurs in a nuclear body called the Histone Locus Body (HLB), a subdomain of the nucleus defined by a concentration of factors necessary for histone gene transcription and pre-mRNA processing. These factors include the scaffolding protein NPAT, essential for histone gene transcription, and FLASH and U7 snRNP, both essential for histone pre-mRNA processing. Histone gene expression is activated by Cyclin E/Cdk2-mediated phosphorylation of NPAT at the G1-S transition. The concentration of factors within the HLB couples transcription with pre-mRNA processing, enhancing the efficiency of histone mRNA biosynthesis. PMID:28059623

Antigenicity of Leishmania braziliensis Histone H1 during Cutaneous Leishmaniasis: Localization of Antigenic Determinants

PubMed Central

Carmelo, Emma; Martínez, Enrique; González, Ana Cristina; Piñero, José Enrique; Patarroyo, Manuel E.; del Castillo, Antonio; Valladares, Basilio

2002-01-01

The humoral immune response against Leishmania braziliensis histone H1 by patients with cutaneous leishmaniasis is described. For this purpose, the protein was purified as a recombinant protein in a prokaryotic expression system and was assayed by enzyme-linked immunosorbent assay (ELISA) with a collection of sera from patients with cutaneous leishmaniasis and Chagas' disease. The assays showed that L. braziliensis histone H1 was recognized by 66% of the serum samples from patients with leishmaniasis and by 40% of the serum samples from patients with Chagas' disease, indicating that it acts as an immunogen during cutaneous leishmaniasis. In order to locate the linear antigenic determinants of this protein, a collection of synthetic peptides covering the L. braziliensis histone H1sequence was tested by ELISA. The experiments showed that the main antigenic determinant is located in the central region of this protein. Our results show that the recombinant L. braziliensis histone H1 is recognized by a significant percentage of serum samples from patients with cutaneous leishmaniasis, but use of this protein as a tool for the diagnosis of cutaneous leishmaniasis is hampered by the cross-reaction with sera from patients with Chagas' disease. PMID:12093677

Antigenicity of Leishmania braziliensis histone H1 during cutaneous leishmaniasis: localization of antigenic determinants.

PubMed

Carmelo, Emma; Martínez, Enrique; González, Ana Cristina; Piñero, José Enrique; Patarroyo, Manuel E; Del Castillo, Antonio; Valladares, Basilio

2002-07-01

The humoral immune response against Leishmania braziliensis histone H1 by patients with cutaneous leishmaniasis is described. For this purpose, the protein was purified as a recombinant protein in a prokaryotic expression system and was assayed by enzyme-linked immunosorbent assay (ELISA) with a collection of sera from patients with cutaneous leishmaniasis and Chagas' disease. The assays showed that L. braziliensis histone H1 was recognized by 66% of the serum samples from patients with leishmaniasis and by 40% of the serum samples from patients with Chagas' disease, indicating that it acts as an immunogen during cutaneous leishmaniasis. In order to locate the linear antigenic determinants of this protein, a collection of synthetic peptides covering the L. braziliensis histone H1sequence was tested by ELISA. The experiments showed that the main antigenic determinant is located in the central region of this protein. Our results show that the recombinant L. braziliensis histone H1 is recognized by a significant percentage of serum samples from patients with cutaneous leishmaniasis, but use of this protein as a tool for the diagnosis of cutaneous leishmaniasis is hampered by the cross-reaction with sera from patients with Chagas' disease.

Histone Hl-DNA interaction. Influence of phosphorylation on the interaction of histone Hl with linear fragmented DNA.

PubMed Central

Glotov, B O; Nikolaev, L G; Kurochkin, S N; Severin, E S

1977-01-01

By measuring the fluorescence polarization of fluorescent histone H1 derivatives complexed with DNA, binding of the histone to DNA was studied as a function of ionic strength in the solution prior to and after the H1 phosphorylation on Ser-37 residue. Fluorescent labels were covalently linked either specifically to Tyr-72 residues or unspecifically to lysine residues in the H1 polypeptide chain. The values of the corresponding rotational relaxation times showed that at low ionic strength all the segments of the H1 molecule were immobilized on binding to DNA. The gradual increasing NaC1 concentration in the solution of H1-DNA complex was accompanied at first by additional retardation of the histone mobility in the complex, and then by progressive release of histone H1 from from the complex which was completed at 0.5-0.6 M NaC1 irrespective of phosphorylation. tat the same time the phosphorylation of histone H1 led to removal of the central and, presumably, N-terminal regions of H1 from DNA. PMID:194228

Napping, development and health from 0 to 5 years: a systematic review.

PubMed

Thorpe, Karen; Staton, Sally; Sawyer, Emily; Pattinson, Cassandra; Haden, Catherine; Smith, Simon

2015-07-01

Duration and quality of sleep affect child development and health. Encouragement of napping in preschool children has been suggested as a health-promoting strategy. The aim of this study is to assess evidence regarding the effects of napping on measures of child development and health. This study is a systematic review of published, original research articles of any design. Children aged 0-5 years. Electronic database search was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and assessment of research quality was carried out following a Grading of Recommendations, Assessment, Development and Evaluations (GRADE) protocol. Twenty-six articles met inclusion criteria. These were of heterogeneous quality; all had observational designs (GRADE-low). Development and health outcomes included salivary cortisol, night sleep, cognition, behaviour, obesity and accidents. The findings regarding cognition, behaviour and health impacts were inconsistent, probably because of variation in age and habitual napping status of the samples. The most consistent finding was an association between napping and later onset, shorter duration and poorer quality of night sleep, with evidence strongest beyond the age of 2 years. Studies were not randomised. Most did not obtain data on the children's habitual napping status or the context of napping. Many were reliant on parent report rather than direct observation or physiological measurement of sleep behaviour. The evidence indicates that beyond the age of 2 years napping is associated with later night sleep onset and both reduced sleep quality and duration. The evidence regarding behaviour, health and cognition is less certain. There is a need for more systematic studies that use stronger designs. In preschool children presenting with sleep problems clinicians should investigate napping patterns. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted

MOF Acetylates the Histone Demethylase LSD1 to Suppress Epithelial-to-Mesenchymal Transition.

PubMed

Luo, Huacheng; Shenoy, Anitha K; Li, Xuehui; Jin, Yue; Jin, Lihua; Cai, Qingsong; Tang, Ming; Liu, Yang; Chen, Hao; Reisman, David; Wu, Lizi; Seto, Edward; Qiu, Yi; Dou, Yali; Casero, Robert A; Lu, Jianrong

2016-06-21

The histone demethylase LSD1 facilitates epithelial-to-mesenchymal transition (EMT) and tumor progression by repressing epithelial marker expression. However, little is known about how its function may be modulated. Here, we report that LSD1 is acetylated in epithelial but not mesenchymal cells. Acetylation of LSD1 reduces its association with nucleosomes, thus increasing histone H3K4 methylation at its target genes and activating transcription. The MOF acetyltransferase interacts with LSD1 and is responsible for its acetylation. MOF is preferentially expressed in epithelial cells and is downregulated by EMT-inducing signals. Expression of exogenous MOF impedes LSD1 binding to epithelial gene promoters and histone demethylation, thereby suppressing EMT and tumor invasion. Conversely, MOF depletion enhances EMT and tumor metastasis. In human cancer, high MOF expression correlates with epithelial markers and a favorable prognosis. These findings provide insight into the regulation of LSD1 and EMT and identify MOF as a critical suppressor of EMT and tumor progression. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Nitric Oxide Modulates Histone Acetylation at Stress Genes by Inhibition of Histone Deacetylases.

PubMed

Mengel, Alexander; Ageeva, Alexandra; Georgii, Elisabeth; Bernhardt, Jörg; Wu, Keqiang; Durner, Jörg; Lindermayr, Christian

2017-02-01

Histone acetylation, which is an important mechanism to regulate gene expression, is controlled by the opposing action of histone acetyltransferases and histone deacetylases (HDACs). In animals, several HDACs are subjected to regulation by nitric oxide (NO); in plants, however, it is unknown whether NO affects histone acetylation. We found that treatment with the physiological NO donor S-nitrosoglutathione (GSNO) increased the abundance of several histone acetylation marks in Arabidopsis (Arabidopsis thaliana), which was strongly diminished in the presence of the NO scavenger 2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide. This increase was likely triggered by NO-dependent inhibition of HDAC activity, since GSNO and S-nitroso-N-acetyl-dl-penicillamine significantly and reversibly reduced total HDAC activity in vitro (in nuclear extracts) and in vivo (in protoplasts). Next, genome-wide H3K9/14ac profiles in Arabidopsis seedlings were generated by chromatin immunoprecipitation sequencing, and changes induced by GSNO, GSNO/2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide or trichostatin A (an HDAC inhibitor) were quantified, thereby identifying genes that display putative NO-regulated histone acetylation. Functional classification of these genes revealed that many of them are involved in the plant defense response and the abiotic stress response. Furthermore, salicylic acid, which is the major plant defense hormone against biotrophic pathogens, inhibited HDAC activity and increased histone acetylation by inducing endogenous NO production. These data suggest that NO affects histone acetylation by targeting and inhibiting HDAC complexes, resulting in the hyperacetylation of specific genes. This mechanism might operate in the plant stress response by facilitating the stress-induced transcription of genes. © 2017 American Society of Plant Biologists. All Rights Reserved.

Napping Reverses Increased Pain Sensitivity Due to Sleep Restriction

PubMed Central

Faraut, Brice; Léger, Damien; Medkour, Terkia; Dubois, Alexandre; Bayon, Virginie; Chennaoui, Mounir; Perrot, Serge

2015-01-01

Study Objective To investigate pain sensitivity after sleep restriction and the restorative effect of napping. Design A strictly controlled randomized crossover study with continuous polysomnography monitoring was performed. Setting Laboratory-based study. Participants 11 healthy male volunteers. Interventions Volunteers attended two three-day sessions: “sleep restriction” alone and “sleep restriction and nap”. Each session involved a baseline night of normal sleep, a night of sleep deprivation and a night of free recovery sleep. Participants were allowed to sleep only from 02:00 to 04:00 during the sleep deprivation night. During the “sleep restriction and nap” session, volunteers took two 30-minute naps, one in the morning and one in the afternoon. Measurements and Results Quantitative sensory testing was performed with heat, cold and pressure, at 10:00 and 16:00, on three areas: the supraspinatus, lower back and thigh. After sleep restriction, quantitative sensory testing revealed differential changes in pain stimuli thresholds, but not in thermal threshold detection: lower back heat pain threshold decreased, pressure pain threshold increased in the supraspinatus area and no change was observed for the thigh. Napping restored responses to heat pain stimuli in the lower back and to pressure stimuli in the supraspinatus area. Conclusions Sleep restriction induces different types of hypersensitivity to pain stimuli in different body areas, consistent with multilevel mechanisms, these changes being reversed by napping. The napping restorative effect on pain thresholds result principally from effects on pain mechanisms, since it was independent of vigilance status. PMID:25723495

Silencing of IFN-stimulated gene transcription is regulated by histone H1 and its chaperone TAF-I.

PubMed

Kadota, Shinichi; Nagata, Kyosuke

2014-07-01

Chromatin structure and its alteration play critical roles in the regulation of transcription. However, the transcriptional silencing mechanism with regard to the chromatin structure at an unstimulated state of the interferon (IFN)-stimulated gene (ISG) remains unclear. Here we investigated the role of template activating factor-I (TAF-I, also known as SET) in ISG transcription. Knockdown (KD) of TAF-I increased ISG transcript and simultaneously reduced the histone H1 level on the ISG promoters during the early stages of transcription after IFN stimulation from the unstimulated state. The transcription factor levels on the ISG promoters were increased in TAF-I KD cells only during the early stages of transcription. Furthermore, histone H1 KD also increased ISG transcript. TAF-I and histone H1 double KD did not show the additive effect in ISG transcription, suggesting that TAF-I and histone H1 may act on the same regulatory pathway to control ISG transcription. In addition, TAF-I KD and histone H1 KD affected the chromatin structure near the ISG promoters. On the basis of these findings, we propose that TAF-I and its target histone H1 are key regulators of the chromatin structure at the ISG promoter to maintain the silent state of ISG transcription. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

The effects of a self-selected nap opportunity on the psychophysiological, performance and subjective measures during a simulated industrial night shift regimen.

PubMed

Davy, Jonathan; Göbel, Matthias

2013-01-01

This study compared the effects of a 1 h self-selected recovery period to those of a standard night shift arrangement (with a total break time of 1-h) over a simulated three-day night shift schedule in a laboratory setting. Results showed that the inclusion of the flexible nap scheme resulted in higher performance output, improvements in physiological strain responses and reduced sleepiness during each night shift and generally over the three-night cycle. Certain variables also revealed the impact of napping compared with the standard rest break condition on the circadian rhythm. The sleep diary records show that the inclusion of the current intervention did not significantly reduce daytime recovery sleep. The results suggest that the potential benefits of flexible napping may outweigh the logistical effort it requires in a workplace environment. Consensus on appropriate napping strategies for shift work remains a challenge. This simulated night shift laboratory study sought to determine the effects of a 1-h self-selected nap opportunity relative to a normal shift set-up. The nap improved performance and decreased sleepiness, without affecting daytime sleep.

Long-Term Single and Joint Effects of Excessive Daytime Napping on the HOMA-IR Index and Glycosylated Hemoglobin: A Prospective Cohort Study.

PubMed

Li, Xue; Pang, Xiuyu; Zhang, Qiao; Qu, Qiannuo; Hou, Zhigang; Liu, Zhipeng; Lv, Lin; Na, Guanqiong; Zhang, Wei; Sun, Changhao; Li, Ying

2016-02-01

This prospective cohort study was conducted to assess the duration of daytime napping and its effect combined with night sleep deprivation on the risk of developing high HOMA-IR (homeostasis model assessment of insulin resistance) index and disadvantageous changes in glycosylated hemoglobin (HbA1c) levels.A total of 5845 diabetes-free subjects (2736 women and 3109 men), 30 to 65 years of age, were targeted for this cohort study since 2008. Multiple adjusted Cox regression models were performed to evaluate the single and joint effects of daytime napping on the risk of an elevated HbA1c level and high HOMA-IR index.After an average of 4.5 years of follow-up, >30 minutes of daytime napping was significantly associated with an increased risk of an elevated HbA1c level (>6.5%) in men and women (all P trend < 0.05). Hazard ratios (HRs) for an HbA1c level between 5.7% and 6.4% were also significant in the entire cohort and women, but nonsignificant in men. HRs (95% confidence interval, CIs) for the high HOMA-IR index in the entire cohort, men, and women were 1.33 (1.10-1.62), 1.46 (1.08-1.98), and 1.47 (1.12-1.91), respectively. The combination of sleep deprivation with no naps or >30 minutes napping and the combination of no sleep deprivation with >30 minutes daytime napping were all associated with an HbA1c level >6.5% (HR = 2.08, 95% CI = 1.24-3.51; HR = 4.00, 95% CI = 2.03-7.90; and HR = 2.05, 95% CI = 1.29-3.27, respectively). No sleep deprivation combined with >30 minutes daytime napping correlated with a high risk of an HbA1c level between 5.7% and 6.4% and high HOMA-IR index (HR = 2.12, 95% CI = 1.48-3.02; and HR = 1.35, 95% CI = 1.10-1.65, respectively).Daytime napping >30 minutes was associated with a high risk of an elevated HbA1c level and high HOMA-IR index. No sleep deprivation combined with napping >30 minutes carries a risk of abnormal glucose metabolism. Sleep deprivation combined with brief daytime napping <30

Daytime Napping, Nighttime Sleeping, and Parkinson Disease

PubMed Central

Gao, Jianjun; Huang, Xuemei; Park, Yikyung; Hollenbeck, Albert; Blair, Aaron; Schatzkin, Arthur; Chen, Honglei

2011-01-01

Preliminary evidence suggests that daytime sleepiness may predate clinical diagnosis of Parkinson disease. The authors examined daytime napping and nighttime sleeping durations, reported in 1996–1997 by 220,934 US NIH-AARP Diet and Health Study participants, in relation to Parkinson disease diagnoses at 3 clinical stages: established (cases diagnosed before 1995, n = 267), recent (1995–1999, n = 396), and prediagnostic (2000 and after, n = 770). Odds ratios and 95% confidence intervals were derived from multivariate logistic regression models. Longer daytime napping was associated with higher odds of Parkinson disease at all 3 clinical stages: the odds ratios comparing long nappers (>1 hour/day) with nonnappers were 3.9 (95% confidence interval: 2.8, 5.6) for established cases, 2.2 (95% confidence interval: 1.7, 3.0) for recent cases, and 1.5 (95% confidence interval: 1.2, 1.9) for prediagnostic cases. Further control for health status or nighttime sleeping duration attenuated the association for established cases but made little difference for recent or prediagnostic cases. In the nighttime sleeping analysis, a clear U-shaped association with Parkinson disease was observed for established cases; however, this association was attenuated markedly for recent cases and disappeared for prediagnostic cases. This study supports the notion that daytime sleepiness, but not nighttime sleeping duration, is one of the early nonmotor symptoms of Parkinson disease. PMID:21402730

Comparing the benefits of caffeine, naps and placebo on verbal, motor and perceptual memory.

PubMed

Mednick, Sara C; Cai, Denise J; Kanady, Jennifer; Drummond, Sean P A

2008-11-03

Caffeine, the world's most common psychoactive substance, is used by approximately 90% of North Americans everyday. Little is known, however, about its benefits for memory. Napping has been shown to increase alertness and promote learning on some memory tasks. We directly compared caffeine (200mg) with napping (60-90min) and placebo on three distinct memory processes: declarative verbal memory, procedural motor skills, and perceptual learning. In the verbal task, recall and recognition for unassociated words were tested after a 7h retention period (with a between-session nap or drug intervention). A second, different, word list was administered post-intervention and memory was tested after a 20min retention period. The non-declarative tasks (finger tapping task (FTT) and texture discrimination task (TDT)) were trained before the intervention and then retested afterwards. Naps enhanced recall of words after a 7h and 20min retention interval relative to both caffeine and placebo. Caffeine significantly impaired motor learning compared to placebo and naps. Napping produced robust perceptual learning compared with placebo; however, naps and caffeine were not significantly different. These findings provide evidence of the limited benefits of caffeine for memory improvement compared with napping. We hypothesize that impairment from caffeine may be restricted to tasks that contain explicit information; whereas strictly implicit learning is less compromised.

Comparing the benefits of Caffeine, Naps and Placebo on Verbal, Motor and Perceptual Memory

PubMed Central

Mednick, Sara C.; Cai, Denise J.; Kanady, Jennifer; Drummond, Sean P.A.

2008-01-01

Caffeine, the world’s most common psychoactive substance, is used by approximately 90% of North Americans everyday. Little is known, however, about its benefits for memory. Napping has been shown to increase alertness and promote learning on some memory tasks. We directly compared caffeine (200mg) with napping (60–90 minutes) and placebo on three distinct memory processes: declarative verbal memory, procedural motor skills, and perceptual learning. In the verbal task, recall and recognition for unassociated words were tested after a 7hr retention period (with a between-session nap or drug intervention). A second, different, word list was administered post-intervention and memory was tested after a 20min retention period. The non-declarative tasks (finger tapping task and texture discrimination task) were trained before the intervention and then retested afterwards. Naps enhanced recall of words after a 7hr and 20min retention interval relative to both caffeine and placebo. Caffeine significantly impaired motor learning compared to placebo and naps. Napping produced robust perceptual learning compared with placebo; however, naps and caffeine were not significantly different. These findings provide evidence of the limited benefits of caffeine for memory improvement compared with napping. We hypothesize that impairment from caffeine may be restricted to tasks that contain explicit information; whereas strictly implicit learning is less compromised. PMID:18554731

Napping in College Students and Its Relationship with Nighttime Sleep

ERIC Educational Resources Information Center

Ye, Lichuan; Hutton Johnson, Stacy; Keane, Kathleen; Manasia, Michael; Gregas, Matt

2015-01-01

Objective: To examine the habit of napping and its relationship with nighttime sleep in college students. Participants: Four hundred and forty undergraduate students who responded to an anonymous online survey in April 2010. Methods: Three questions were asked to determine the frequency, length, and timing of napping during the past month. Sleep…

Characterization of Histone H2A Derived Antimicrobial Peptides, Harriottins, from Sicklefin Chimaera Neoharriotta pinnata (Schnakenbeck, 1931) and Its Evolutionary Divergence with respect to CO1 and Histone H2A.

PubMed

Sathyan, Naveen; Philip, Rosamma; Chaithanya, E R; Anil Kumar, P R; Sanjeevan, V N; Singh, I S Bright

2013-01-01

Antimicrobial peptides (AMPs) are humoral innate immune components of fishes that provide protection against pathogenic infections. Histone derived antimicrobial peptides are reported to actively participate in the immune defenses of fishes. Present study deals with identification of putative antimicrobial sequences from the histone H2A of sicklefin chimaera, Neoharriotta pinnata. A 52 amino acid residue termed Harriottin-1, a 40 amino acid Harriottin-2, and a 21 mer Harriottin-3 were identified to possess antimicrobial sequence motif. Physicochemical properties and molecular structure of Harriottins are in agreement with the characteristic features of antimicrobial peptides, indicating its potential role in innate immunity of sicklefin chimaera. The histone H2A sequence of sicklefin chimera was found to differ from previously reported histone H2A sequences. Phylogenetic analysis based on histone H2A and cytochrome oxidase subunit-1 (CO1) gene revealed N. pinnata to occupy an intermediate position with respect to invertebrates and vertebrates.

Characterization of Histone H2A Derived Antimicrobial Peptides, Harriottins, from Sicklefin Chimaera Neoharriotta pinnata (Schnakenbeck, 1931) and Its Evolutionary Divergence with respect to CO1 and Histone H2A

PubMed Central

Sathyan, Naveen; Philip, Rosamma; Chaithanya, E. R.; Anil Kumar, P. R.; Sanjeevan, V. N.; Singh, I. S. Bright

2013-01-01

Antimicrobial peptides (AMPs) are humoral innate immune components of fishes that provide protection against pathogenic infections. Histone derived antimicrobial peptides are reported to actively participate in the immune defenses of fishes. Present study deals with identification of putative antimicrobial sequences from the histone H2A of sicklefin chimaera, Neoharriotta pinnata. A 52 amino acid residue termed Harriottin-1, a 40 amino acid Harriottin-2, and a 21 mer Harriottin-3 were identified to possess antimicrobial sequence motif. Physicochemical properties and molecular structure of Harriottins are in agreement with the characteristic features of antimicrobial peptides, indicating its potential role in innate immunity of sicklefin chimaera. The histone H2A sequence of sicklefin chimera was found to differ from previously reported histone H2A sequences. Phylogenetic analysis based on histone H2A and cytochrome oxidase subunit-1 (CO1) gene revealed N. pinnata to occupy an intermediate position with respect to invertebrates and vertebrates. PMID:27398241

Asymmetric binding of histone H1 stabilizes MMTV nucleosomes and the interaction of progesterone receptor with the exposed HRE.

PubMed

Vicent, Guillermo P; Meliá, María J; Beato, Miguel

2002-11-29

Packaging of mouse mammary tumor virus (MMTV) promoter sequences in nucleosomes modulates access of DNA binding proteins and influences the interaction among DNA bound transcription factors. Here we analyze the binding of histone H1 to MMTV mononucleosomes assembled with recombinant histones and study its influence on nucleosome structure and stability as well as on progesterone receptor (PR) binding to the hormone responsive elements (HREs). The MMTV nucleosomes can be separated into three main populations, two of which exhibited precise translational positioning. Histone H1 bound preferentially to the 5' distal nucleosomal DNA protecting additional 27-28 nt from digestion by micrococcal nuclease. Binding of histone H1 was unaffected by prior crosslinking of protein and DNA in nucleosomes with formaldehyde. Neither the translational nor the rotational nucleosome positioning was altered by histone H1 binding, but the nucleosomes were stabilized as judged by the kinetics of nuclease cleavage. Unexpectedly, binding of recombinant PR to the exposed distal HRE-I in nucleosomes was enhanced in the presence of histone H1, as demonstrated by band shift and footprinting experiments. This enhanced PR affinity may contribute to the reported positive effect of histone H1 on the hormonal activation of MMTV reporter genes.

Isolation and analysis of linker histones across cellular compartments

PubMed Central

Harshman, Sean W.; Chen, Michael M.; Branson, Owen E.; Jacob, Naduparambil K.; Johnson, Amy J.; Byrd, John C.; Freitas, Michael A.

2013-01-01

Analysis of histones, especially histone H1, is severely limited by immunological reagent availability. This paper describes the application of cellular fractionation with LC-MS for profiling histones in the cytosol and upon chromatin. First, we show that linker histones enriched by cellular fractionation gives less nuclear contamination and higher histone content than when prepared by nuclei isolation. Second, we profiled the soluble linker histones throughout the cell cycle revealing phosphorylation increases as cells reach mitosis. Finally, we monitored histone H1.2–H1.5 translocation to the cytosol in response to the CDK inhibitor flavopiridol in primary CLL cells treated ex vivo. Data shows all H1 variants translocate in response to drug treatment with no specific order to their cytosolic appearance. The results illustrate the utility of cellular fractionation in conjunction with LC-MS for the analysis of histone H1 throughout the cell. PMID:24013129

Histone H1 functions as a stimulatory factor in backup pathways of NHEJ

PubMed Central

Rosidi, Bustanur; Wang, Minli; Wu, Wenqi; Sharma, Aparna; Wang, Huichen; Iliakis, George

2008-01-01

DNA double-strand breaks (DSBs) induced in the genome of higher eukaryotes by ionizing radiation (IR) are predominantly removed by two pathways of non-homologous end-joining (NHEJ) termed D-NHEJ and B-NHEJ. While D-NHEJ depends on the activities of the DNA-dependent protein kinase (DNA-PK) and DNA ligase IV/XRCC4/XLF, B-NHEJ utilizes, at least partly, DNA ligase III/XRCC1 and PARP-1. Using in vitro end-joining assays and protein fractionation protocols similar to those previously applied for the characterization of DNA ligase III as an end-joining factor, we identify here histone H1 as an additional putative NHEJ factor. H1 strongly enhances DNA-end joining and shifts the product spectrum from circles to multimers. While H1 enhances the DNA-end-joining activities of both DNA Ligase IV and DNA Ligase III, the effect on ligase III is significantly stronger. Histone H1 also enhances the activity of PARP-1. Since histone H1 has been shown to counteract D-NHEJ, these observations and the known functions of the protein identify it as a putative alignment factor operating preferentially within B-NHEJ. PMID:18250087

Histone acetyltransferase TGF-1 regulates Trichoderma atroviride secondary metabolism and mycoparasitism.

PubMed

Gómez-Rodríguez, Elida Yazmín; Uresti-Rivera, Edith Elena; Patrón-Soberano, Olga Araceli; Islas-Osuna, María Auxiliadora; Flores-Martínez, Alberto; Riego-Ruiz, Lina; Rosales-Saavedra, María Teresa; Casas-Flores, Sergio

2018-01-01

Some filamentous fungi of the Trichoderma genus are used as biocontrol agents against airborne and soilborne phytopathogens. The proposed mechanism by which Trichoderma spp. antagonizes phytopathogens is through the release of lytic enzymes, antimicrobial compounds, mycoparasitism, and the induction of systemic disease-resistance in plants. Here we analyzed the role of TGF-1 (Trichoderma Gcn Five-1), a histone acetyltransferase of Trichoderma atroviride, in mycoparasitism and antibiosis against the phytopathogen Rhizoctonia solani. Trichostatin A (TSA), a histone deacetylase inhibitor that promotes histone acetylation, slightly affected T. atroviride and R. solani growth, but not the growth of the mycoparasite over R. solani. Application of TSA to the liquid medium induced synthesis of antimicrobial compounds. Expression analysis of the mycoparasitism-related genes ech-42 and prb-1, which encode an endochitinase and a proteinase, as well as the secondary metabolism-related genes pbs-1 and tps-1, which encode a peptaibol synthetase and a terpene synthase, respectively, showed that they were regulated by TSA. A T. atroviride strain harboring a deletion of tgf-1 gene showed slow growth, thinner and less branched hyphae than the wild-type strain, whereas its ability to coil around the R. solani hyphae was not affected. Δtgf-1 presented a diminished capacity to grow over R. solani, but the ability of its mycelium -free culture filtrates (MFCF) to inhibit the phytopathogen growth was enhanced. Intriguingly, addition of TSA to the culture medium reverted the enhanced inhibition growth of Δtgf-1 MFCF on R. solani at levels compared to the wild-type MFCF grown in medium amended with TSA. The presence of R. solani mycelium in the culture medium induced similar proteinase activity in a Δtgf-1 compared to the wild-type, whereas the chitinolytic activity was higher in a Δtgf-1 mutant in the absence of R. solani, compared to the parental strain. Expression of mycoparasitism

Histone acetyltransferase TGF-1 regulates Trichoderma atroviride secondary metabolism and mycoparasitism

PubMed Central

Patrón-Soberano, Olga Araceli; Islas-Osuna, María Auxiliadora; Flores-Martínez, Alberto; Riego-Ruiz, Lina; Rosales-Saavedra, María Teresa

2018-01-01

Some filamentous fungi of the Trichoderma genus are used as biocontrol agents against airborne and soilborne phytopathogens. The proposed mechanism by which Trichoderma spp. antagonizes phytopathogens is through the release of lytic enzymes, antimicrobial compounds, mycoparasitism, and the induction of systemic disease-resistance in plants. Here we analyzed the role of TGF-1 (Trichoderma Gcn Five-1), a histone acetyltransferase of Trichoderma atroviride, in mycoparasitism and antibiosis against the phytopathogen Rhizoctonia solani. Trichostatin A (TSA), a histone deacetylase inhibitor that promotes histone acetylation, slightly affected T. atroviride and R. solani growth, but not the growth of the mycoparasite over R. solani. Application of TSA to the liquid medium induced synthesis of antimicrobial compounds. Expression analysis of the mycoparasitism-related genes ech-42 and prb-1, which encode an endochitinase and a proteinase, as well as the secondary metabolism-related genes pbs-1 and tps-1, which encode a peptaibol synthetase and a terpene synthase, respectively, showed that they were regulated by TSA. A T. atroviride strain harboring a deletion of tgf-1 gene showed slow growth, thinner and less branched hyphae than the wild-type strain, whereas its ability to coil around the R. solani hyphae was not affected. Δtgf-1 presented a diminished capacity to grow over R. solani, but the ability of its mycelium -free culture filtrates (MFCF) to inhibit the phytopathogen growth was enhanced. Intriguingly, addition of TSA to the culture medium reverted the enhanced inhibition growth of Δtgf-1 MFCF on R. solani at levels compared to the wild-type MFCF grown in medium amended with TSA. The presence of R. solani mycelium in the culture medium induced similar proteinase activity in a Δtgf-1 compared to the wild-type, whereas the chitinolytic activity was higher in a Δtgf-1 mutant in the absence of R. solani, compared to the parental strain. Expression of mycoparasitism

Naps promote flexible memory retrieval in 12-month-old infants.

PubMed

Konrad, Carolin; Seehagen, Sabine; Schneider, Silvia; Herbert, Jane S

2016-11-01

Flexibility in applying existing knowledge to similar cues is a corner stone of memory development in infants. Here, we examine the effect of sleep on the flexibility of memory retrieval using a deferred imitation paradigm. Forty-eight 12-month-old infants were randomly assigned to either a nap or a no-nap demonstration condition (scheduled around their natural daytime sleep schedule) or to a baseline control condition. In the demonstration conditions, infants watched an experimenter perform three target actions on a hand puppet. Immediately afterwards, infants were allowed to practice the target actions three times. In a test session 4-hr later, infants were given the opportunity to reproduce the actions with a novel hand puppet differing in color from the puppet used during the demonstration session. Only infants in the nap-condition performed significantly more target actions than infants in the baseline control condition. Furthermore, they were faster to carry out the first target action than infants in the no-nap condition. We conclude that sleep had a facilitative effect on infants' flexibility of memory retrieval. © 2016 Wiley Periodicals, Inc.

Delayed benefit of naps on motor learning in preschool children.

PubMed

Desrochers, Phillip C; Kurdziel, Laura B F; Spencer, Rebecca M C

2016-03-01

Sleep benefits memory consolidation across a variety of domains in young adults. However, while declarative memories benefit from sleep in young children, such improvements are not consistently seen for procedural skill learning. Here we examined whether performance improvements on a procedural task, although not immediately observed, are evident after a longer delay when augmented by overnight sleep (24 h after learning). We trained 47 children, aged 33-71 months, on a serial reaction time task and, using a within-subject design, evaluated performance at three time points: immediately after learning, after a daytime nap (nap condition) or equivalent wake opportunity (wake condition), and 24 h after learning. Consistent with previous studies, performance improvements following the nap did not differ from performance improvements following an equivalent interval spent awake. However, significant benefits of the nap were found when performance was assessed 24 h after learning. This research demonstrates that motor skill learning is benefited by sleep, but that this benefit is only evident after an extended period of time.

Sleep Duration and Midday Napping with 5-Year Incidence and Reversion of Metabolic Syndrome in Middle-Aged and Older Chinese.

PubMed

Yang, Liangle; Xu, Zengguang; He, Meian; Yang, Handong; Li, Xiulou; Min, Xinwen; Zhang, Ce; Xu, Chengwei; Angileri, Francesca; Légaré, Sébastien; Yuan, Jing; Miao, Xiaoping; Guo, Huan; Yao, Ping; Wu, Tangchun; Zhang, Xiaomin

2016-11-01

Prospective evidence on the association of sleep duration and midday napping with metabolic syndrome (MetS) is limited. We aimed to examine the associations of sleep duration and midday napping with risk of incidence and reversion of MetS and its components among a middle-aged and older Chinese population. We included 14,399 subjects from the Dongfeng-Tongji (DFTJ) Cohort Study (2008-2013) who were free of coronary heart disease, stroke, and cancer at baseline. Baseline data were obtained by questionnaires and health examinations. Odds ratios (ORs) and 95% confidence interval (CI) were derived from multivariate logistic regression models. After controlling for potential covariates, longer sleep duration (≥ 9 h) was associated with a higher risk of MetS incidence (OR, 1.29; 95% CI, 1.08-1.55) and lower reversion of MetS (OR, 0.80; 95% CI, 0.66-0.96) compared with sleep duration of 7 to < 8 h; whereas shorter sleep duration (< 6 h) was not related to incidence or reversion of MetS. For midday napping, subjects with longer napping (≥ 90 min) was also associated with a higher risk of MetS incidence and a lower risk of MetS reversion compared with those with napping of 1 to < 30 min (OR, 1.48; 95% CI, 1.05-2.10 and OR, 0.70; 95% CI, 0.52-0.94, respectively). Significance for incidence or reversion of certain MetS components remained in shorter and longer sleepers but disappeared across napping categories. Both longer sleep duration and longer midday napping were potential risk factors for MetS incidence, and concurrently exert adverse effects on MetS reversion. © 2016 Associated Professional Sleep Societies, LLC.

Self-reported sleep and nap habits and risk of mortality in a large cohort of older women.

PubMed

Stone, Katie L; Ewing, Susan K; Ancoli-Israel, Sonia; Ensrud, Kristine E; Redline, Susan; Bauer, Douglas C; Cauley, Jane A; Hillier, Teresa A; Cummings, Steven R

2009-04-01

To determine the association between self-reported sleep and nap habits and mortality in a large cohort of older women. Study of Osteoporotic Fractures prospective cohort study. Four communities within the United States. Eight thousand one hundred one Caucasian women aged 69 and older (mean age 77.0). Sleep and nap habits were assessed using a questionnaire at the fourth clinic visit (1993/94). Deaths during 7 years of follow-up were confirmed with death certificates. Underlying cause of death was assigned according to the International Classification of Diseases, Ninth Revision, Clinical Modification. In multivariate models, women who reported napping daily were 44% more likely to die from any cause (95% confidence interval (CI)=1.23-1.67), 58% more likely to die from cardiovascular causes (95% CI=1.25-2.00), and 59% more likely to die from noncardiovascular noncancer causes (95% CI=1.24-2.03) than women who did not nap daily. This relationship remained significant in relatively healthy women (those who reported no comorbidities). Women who slept 9 to 10 hours per 24 hours were at greater risk of death from cardiovascular and other (noncardiovascular, noncancer) causes than those who reported sleeping 8 to 9 hours. Older women who reported napping daily or sleeping at least 9 hours per 24 hours are at greater risk of death from all causes except cancer. Future research could determine whether specific sleep disorders contribute to these relationships.

The Cac2 subunit is essential for productive histone binding and nucleosome assembly in CAF-1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mattiroli, Francesca; Gu, Yajie; Balsbaugh, Jeremy L.

Nucleosome assembly following DNA replication controls epigenome maintenance and genome integrity. Chromatin assembly factor 1 (CAF-1) is the histone chaperone responsible for histone (H3-H4)2 deposition following DNA synthesis. Structural and functional details for this chaperone complex and its interaction with histones are slowly emerging. Using hydrogen-deuterium exchange coupled to mass spectrometry, combined with in vitro and in vivo mutagenesis studies, we identified the regions involved in the direct interaction between the yeast CAF-1 subunits, and mapped the CAF-1 domains responsible for H3-H4 binding. The large subunit, Cac1 organizes the assembly of CAF-1. Strikingly, H3-H4 binding is mediated by a compositemore » interface, shaped by Cac1-bound Cac2 and the Cac1 acidic region. Cac2 is indispensable for productive histone binding, while deletion of Cac3 has only moderate effects on H3-H4 binding and nucleosome assembly. These results define direct structural roles for yeast CAF-1 subunits and uncover a previously unknown critical function of the middle subunit in CAF-1.« less

Daytime napping, sleep duration and serum C reactive protein: a population-based cohort study

PubMed Central

Leng, Yue; Ahmadi-Abhari, Sara; Wainwright, Nick W J; Cappuccio, Francesco P; Surtees, Paul G; Luben, Robert; Brayne, Carol; Khaw, Kay-Tee

2014-01-01

Objectives To explore whether daytime napping and sleep duration are linked to serum C reactive protein (CRP), a pro-inflammatory marker, in an older aged British population. Design Cross-sectional study. Setting European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk study. Participants A total of 5018 men and women aged 48–92 years reported their sleep habits and had serum CRP levels measured. Outcome and measures CRP was measured (mg/L) during 2006–2011 in fresh blood samples using high-sensitivity methods. Participants reported napping habits during 2002–2004, and reported sleep quantity during 2006–2007. Multivariable linear regression models were used to examine the association between napping and log-transformed CRP, and geometric mean CRP levels were calculated. Results After adjustment for age and sex, those who reported napping had 10% higher CRP levels compared with those not napping. The association was attenuated but remained borderline significant (β=0.05 (95% CI 0.00 to 0.10)) after further adjustment for social class, education, marital status, body mass index, physical activity, smoking, alcohol intake, self-reported health, pre-existing diseases, systolic blood pressure, hypnotic drug use, depression and in women-only hormone replacement therapy use. The geometric means (95% CI) of CRP levels were 2.38 (2.29 to 2.47) mg/L and 2.26 (2.21 to 2.32) mg/L for those who reported napping and no napping, respectively. A U-shaped association was observed between time spent in bed at night and CRP levels, and nighttime sleep duration was not associated with serum CRP levels. The association between napping and CRP was stronger for older participants, and among extremes of time spent in bed at night. Conclusions Daytime napping was associated with increased CRP levels in an older aged British population. Further studies are needed to determine whether daytime napping is a cause for systemic inflammation, or if it is a symptom

Histone H1 is essential for mitotic chromosome architecture and segregation in Xenopus laevis egg extracts

PubMed Central

Maresca, Thomas J.; Freedman, Benjamin S.; Heald, Rebecca

2005-01-01

During cell division, condensation and resolution of chromosome arms and the assembly of a functional kinetochore at the centromere of each sister chromatid are essential steps for accurate segregation of the genome by the mitotic spindle, yet the contribution of individual chromatin proteins to these processes is poorly understood. We have investigated the role of embryonic linker histone H1 during mitosis in Xenopus laevis egg extracts. Immunodepletion of histone H1 caused the assembly of aberrant elongated chromosomes that extended off the metaphase plate and outside the perimeter of the spindle. Although functional kinetochores assembled, aligned, and exhibited poleward movement, long and tangled chromosome arms could not be segregated in anaphase. Histone H1 depletion did not significantly affect the recruitment of known structural or functional chromosomal components such as condensins or chromokinesins, suggesting that the loss of H1 affects chromosome architecture directly. Thus, our results indicate that linker histone H1 plays an important role in the structure and function of vertebrate chromosomes in mitosis. PMID:15967810

Histone methyltransferase Ash1L mediates activity-dependent repression of neurexin-1α

PubMed Central

Zhu, Τao; Liang, Chen; Li, Dongdong; Tian, Miaomiao; Liu, Sanxiong; Gao, Guanjun; Guan, Ji-Song

2016-01-01

Activity-dependent transcription is critical for the regulation of long-term synaptic plasticity and plastic rewiring in the brain. Here, we report that the transcription of neurexin1α (nrxn1α), a presynaptic adhesion molecule for synaptic formation, is regulated by transient neuronal activation. We showed that 10 minutes of firing at 50 Hz in neurons repressed the expression of nrxn1α for 24 hours in a primary cortical neuron culture through a transcriptional repression mechanism. By performing a screening assay using a synthetic zinc finger protein (ZFP) to pull down the proteins enriched near the nrxn1α promoter region in vivo, we identified that Ash1L, a histone methyltransferase, is enriched in the nrxn1α promoter. Neuronal activity triggered binding of Ash1L to the promoter and enriched the histone marker H3K36me2 at the nrxn1α promoter region. Knockout of Ash1L in mice completely abolished the activity-dependent repression of nrxn1α. Taken together, our results reveal that a novel process of activity-dependent transcriptional repression exists in neurons and that Ash1L mediates the long-term repression of nrxn1α, thus implicating an important role for epigenetic modification in brain functioning. PMID:27229316

The effects of nighttime napping on sleep, sleep inertia, and performance during simulated 16 h night work: a pilot study.

PubMed

Oriyama, Sanae; Miyakoshi, Yukiko

2018-03-27

This study aimed to elucidate the effects of two naps taken at night on morning waking state and performance. The participants were 12 women. The experiment was performed in a laboratory over 2 days (16:00-09:00). In this crossover comparative study, three experimental nap conditions were used (naps from 22:30 to 00:00 and from 02:30 to 03:00 (22:30-NAP), 00:30 to 02:00 and 04:30 to 05:00 (00:30-NAP), and no naps (NO-NAP), respectively). Measurement items were a Visual Analog Scale for sleepiness and fatigue, the Psychomotor Vigilance Test (PVT), and single-digit addition calculations (10 min) every hour for 18 h from 16:00 to 09:00, excluding nap times. Sleep inertia and sleepiness were noted directly after napping. Less sleepiness and fatigue were noted in the nap groups between 06:00 and 09:00 in the morning than in the NO-NAP condition and PVT response times were faster. Since participants in the nap groups were able to conduct more single-digit addition calculations, the performance of these groups appeared to be superior to that of the NO-NAP condition. Furthermore, the performance of calculations was significantly better in the 00:30-NAP than in the 22:30-NAP. Taking two naps during a simulated night shift helps improve sleepiness and fatigue and maintain performance. Taking a nap in the early morning appears to be promising for improving the waking state.

Objective measurement of daytime napping, cognitive dysfunction and subjective sleepiness in Parkinson's disease.

PubMed

Bolitho, Samuel J; Naismith, Sharon L; Salahuddin, Pierre; Terpening, Zoe; Grunstein, Ron R; Lewis, Simon J G

2013-01-01

Sleep-wake disturbances and concomitant cognitive dysfunction in Parkinson's disease (PD) contribute significantly to morbidity in patients and their carers. Subjectively reported daytime sleep disturbance is observed in over half of all patients with PD and has been linked to executive cognitive dysfunction. The current study used daytime actigraphy, a novel objective measure of napping and related this to neuropsychological performance in a sample of PD patients and healthy, age and gender-matched controls. Furthermore this study aimed to identify patients with PD who may benefit from pharmacologic and behavioural intervention to improve these symptoms. Eighty-five PD patients and 21 healthy, age-matched controls completed 14 days of wrist actigraphy within two weeks of neuropsychological testing. Objective napping measures were derived from actigraphy using a standardised protocol and subjective daytime sleepiness was recorded by the previously validated Epworth Sleepiness Scale. Patients with PD had a 225% increase in the mean nap time per day (minutes) as recorded by actigraphy compared to age matched controls (39.2 ± 35.2 vs. 11.5 ± 11.0 minutes respectively, p < 0.001). Significantly, differences in napping duration between patients, as recorded by actigraphy were not distinguished by their ratings on the subjective measurement of excessive daytime sleepiness. Finally, those patients with excessive daytime napping showed greater cognitive deficits in the domains of attention, semantic verbal fluency and processing speed. This study confirms increased levels of napping in PD, a finding that is concordant with subjective reports. However, subjective self-report measures of excessive daytime sleepiness do not robustly identify excessive napping in PD. Fronto-subcortical cognitive dysfunction was observed in those patients who napped excessively. Furthermore, this study suggests that daytime actigraphy, a non-invasive and inexpensive objective measure of

The Saccharomyces cerevisiae Cdk8 Mediator Represses AQY1 Transcription by Inhibiting Set1p-Dependent Histone Methylation.

PubMed

Law, Michael J; Finger, Michael A

2017-03-10

In the budding yeast Saccharomyces cerevisiae , nutrient depletion induces massive transcriptional reprogramming that relies upon communication between transcription factors, post-translational histone modifications, and the RNA polymerase II holoenzyme complex. Histone H3Lys4 methylation (H3Lys4 me), regulated by the Set1p-containing COMPASS methyltransferase complex and Jhd2p demethylase, is one of the most well-studied histone modifications. We previously demonstrated that the RNA polymerase II mediator components cyclin C-Cdk8p inhibit locus-specific H3Lys4 3me independently of Jhd2p Here, we identify loci subject to cyclin C- and Jhd2p-dependent histone H3Lys4 3me inhibition using chromatin immunoprecipitation (ChIP)-seq. We further characterized the independent and combined roles of cyclin C and Jhd2p in controlling H3Lys4 3me and transcription in response to fermentable and nonfermentable carbon at multiple loci. These experiments suggest that H3Lys4 3me alone is insufficient to induce transcription. Interestingly, we identified an unexpected role for cyclin C-Cdk8p in repressing AQY1 transcription, an aquaporin whose expression is normally induced during nutrient deprivation. These experiments, combined with previous work in other labs, support a two-step model in which cyclin C-Cdk8p mediate AQY1 transcriptional repression by stimulating transcription factor proteolysis and preventing Set1p recruitment to the AQY1 locus. Copyright © 2017 Law and Finger.

Gender differences in nighttime sleep and daytime napping as predictors of mortality in older adults: the Rancho Bernardo study.

PubMed

Jung, Kyu-In; Song, Chan-Hee; Ancoli-Israel, Sonia; Barrett-Connor, Elizabeth

2013-01-01

Many studies suggest optimal sleep duration for survival is 7-8h/night. We report the gender-specific independent association of all-cause mortality with nighttime sleep and daytime nap duration in older adults who were followed for up to 19years. Between 1984 and 1987, 2001 community-dwelling, mostly retired, adults (1112 women), age 60-96years, answered questions about health, mood, medications, life-style, daytime napping, and nighttime sleep duration. Vital status was confirmed for 96% through July 2001. At baseline, men reported significantly longer nighttime sleep and daytime napping than women. In both men and women, nighttime sleep <6h was associated with depressed mood and sleep-related medication, and ⩾9h was associated with more alcohol consumption. Napping ⩾30min was associated with prevalent depressed mood, coronary heart disease, and cancer. Of the group, 61% died over the next 19years, at an average age of 85.6years. Mortality risk was lowest among those sleeping 7-7.9h/night in both men and women. Multiple-adjusted analyses showed that increased mortality was associated with nighttime sleep ⩾9h in women (HR 1.51: 95% CI=1.05-2.18), and with daytime napping ⩾30min in men (HR 1.28: 95% CI, 1.00-1.64). Mechanisms for these differences are unknown. Copyright © 2012 Elsevier B.V. All rights reserved.

The Association between Daytime Napping and Cognitive Functioning in Chronic Fatigue Syndrome

PubMed Central

Gotts, Zoe M.; Ellis, Jason G.; Deary, Vincent; Barclay, Nicola; Newton, Julia L.

2015-01-01

Objectives The precise relationship between sleep and physical and mental functioning in chronic fatigue syndrome (CFS) has not been examined directly, nor has the impact of daytime napping. This study aimed to examine self-reported sleep in patients with CFS and explore whether sleep quality and daytime napping, specific patient characteristics (gender, illness length) and levels of anxiety and depression, predicted daytime fatigue severity, levels of daytime sleepiness and cognitive functioning, all key dimensions of the illness experience. Methods 118 adults meeting the 1994 CDC case criteria for CFS completed a standardised sleep diary over 14 days. Momentary functional assessments of fatigue, sleepiness, cognition and mood were completed by patients as part of usual care. Levels of daytime functioning and disability were quantified using symptom assessment tools, measuring fatigue (Chalder Fatigue Scale), sleepiness (Epworth Sleepiness Scale), cognitive functioning (Trail Making Test, Cognitive Failures Questionnaire), and mood (Hospital Anxiety and Depression Scale). Results Hierarchical Regressions demonstrated that a shorter time since diagnosis, higher depression and longer wake time after sleep onset predicted 23.4% of the variance in fatigue severity (p <.001). Being male, higher depression and more afternoon naps predicted 25.6% of the variance in objective cognitive dysfunction (p <.001). Higher anxiety and depression and morning napping predicted 32.2% of the variance in subjective cognitive dysfunction (p <.001). When patients were classified into groups of mild and moderate sleepiness, those with longer daytime naps, those who mainly napped in the afternoon, and those with higher levels of anxiety, were more likely to be in the moderately sleepy group. Conclusions Napping, particularly in the afternoon is associated with poorer cognitive functioning and more daytime sleepiness in CFS. These findings have clinical implications for symptom management

The association between daytime napping and cognitive functioning in chronic fatigue syndrome.

PubMed

Gotts, Zoe M; Ellis, Jason G; Deary, Vincent; Barclay, Nicola; Newton, Julia L

2015-01-01

The precise relationship between sleep and physical and mental functioning in chronic fatigue syndrome (CFS) has not been examined directly, nor has the impact of daytime napping. This study aimed to examine self-reported sleep in patients with CFS and explore whether sleep quality and daytime napping, specific patient characteristics (gender, illness length) and levels of anxiety and depression, predicted daytime fatigue severity, levels of daytime sleepiness and cognitive functioning, all key dimensions of the illness experience. 118 adults meeting the 1994 CDC case criteria for CFS completed a standardised sleep diary over 14 days. Momentary functional assessments of fatigue, sleepiness, cognition and mood were completed by patients as part of usual care. Levels of daytime functioning and disability were quantified using symptom assessment tools, measuring fatigue (Chalder Fatigue Scale), sleepiness (Epworth Sleepiness Scale), cognitive functioning (Trail Making Test, Cognitive Failures Questionnaire), and mood (Hospital Anxiety and Depression Scale). Hierarchical Regressions demonstrated that a shorter time since diagnosis, higher depression and longer wake time after sleep onset predicted 23.4% of the variance in fatigue severity (p <.001). Being male, higher depression and more afternoon naps predicted 25.6% of the variance in objective cognitive dysfunction (p <.001). Higher anxiety and depression and morning napping predicted 32.2% of the variance in subjective cognitive dysfunction (p <.001). When patients were classified into groups of mild and moderate sleepiness, those with longer daytime naps, those who mainly napped in the afternoon, and those with higher levels of anxiety, were more likely to be in the moderately sleepy group. Napping, particularly in the afternoon is associated with poorer cognitive functioning and more daytime sleepiness in CFS. These findings have clinical implications for symptom management strategies.

Sleep Duration and Midday Napping with 5-Year Incidence and Reversion of Metabolic Syndrome in Middle-Aged and Older Chinese

PubMed Central

Yang, Liangle; Xu, Zengguang; He, Meian; Yang, Handong; Li, Xiulou; Min, Xinwen; Zhang, Ce; Xu, Chengwei; Angileri, Francesca; Légaré, Sébastien; Yuan, Jing; Miao, Xiaoping; Guo, Huan; Yao, Ping; Wu, Tangchun; Zhang, Xiaomin

2016-01-01

Study Objectives: Prospective evidence on the association of sleep duration and midday napping with metabolic syndrome (MetS) is limited. We aimed to examine the associations of sleep duration and midday napping with risk of incidence and reversion of MetS and its components among a middle-aged and older Chinese population. Methods: We included 14,399 subjects from the Dongfeng-Tongji (DFTJ) Cohort Study (2008–2013) who were free of coronary heart disease, stroke, and cancer at baseline. Baseline data were obtained by questionnaires and health examinations. Odds ratios (ORs) and 95% confidence interval (CI) were derived from multivariate logistic regression models. Results: After controlling for potential covariates, longer sleep duration (≥ 9 h) was associated with a higher risk of MetS incidence (OR, 1.29; 95% CI, 1.08–1.55) and lower reversion of MetS (OR, 0.80; 95% CI, 0.66–0.96) compared with sleep duration of 7 to < 8 h; whereas shorter sleep duration (< 6 h) was not related to incidence or reversion of MetS. For midday napping, subjects with longer napping (≥ 90 min) was also associated with a higher risk of MetS incidence and a lower risk of MetS reversion compared with those with napping of 1 to < 30 min (OR, 1.48; 95% CI, 1.05–2.10 and OR, 0.70; 95% CI, 0.52–0.94, respectively). Significance for incidence or reversion of certain MetS components remained in shorter and longer sleepers but disappeared across napping categories. Conclusions: Both longer sleep duration and longer midday napping were potential risk factors for MetS incidence, and concurrently exert adverse effects on MetS reversion. Citation: Yang L, Xu Z, He M, Yang H, Li X, Min X, Zhang C, Xu C, Angileri F, Légaré S, Yuan J, Miao X, Guo H, Yao P, Wu T, Zhang X. Sleep duration and midday napping with 5-year incidence and reversion of metabolic syndrome in middle-aged and older Chinese. SLEEP 2016;39(11):1911–1918. PMID:27450688

Snipper, an Eri1 homologue, affects histone mRNA abundance and is crucial for normal Drosophila melanogaster development.

PubMed

Alexiadis, Anastasios; Delidakis, Christos; Kalantidis, Kriton

2017-07-01

The conserved 3'-5' RNA exonuclease ERI1 is implicated in RNA interference inhibition, 5.8S rRNA maturation and histone mRNA maturation and turnover. The single ERI1 homologue in Drosophila melanogaster Snipper (Snp) is a 3'-5' exonuclease, but its in vivo function remains elusive. Here, we report Snp requirement for normal Drosophila development, since its perturbation leads to larval arrest and tissue-specific downregulation results in abnormal tissue development. Additionally, Snp directly interacts with histone mRNA, and its depletion results in drastic reduction in histone transcript levels. We propose that Snp protects the 3'-ends of histone mRNAs and upon its absence, histone transcripts are readily degraded. This in turn may lead to cell cycle delay or arrest, causing growth arrest and developmental perturbations. © 2017 Federation of European Biochemical Societies.

Self-Reported Sleep and Nap Habits and Risk of Mortality in a Large Cohort of Older Women

PubMed Central

Stone, Katie L.; Ewing, Susan K.; Ancoli-Israel, Sonia; Ensrud, Kristine E.; Redline, Susan; Bauer, Douglas C.; Cauley, Jane A.; Hillier, Teresa A.; Cummings, Steven R.

2010-01-01

Objectives To determine the association between self-reported sleep and nap habits and mortality in a large cohort of older women. Design Study of Osteoporotic Fractures prospective cohort study. Setting Four communities within the United States. Participants Eight thousand one hundred one Caucasian women aged 69 and older (mean age =77.0 years). Measurements Sleep and nap habits were assessed using a questionnaire at the fourth clinic visit (1993/94). Deaths during seven years of follow-up were identified by contacts every 4 months and confirmed with death certificates. Underlying cause of death was assigned according to the ICD-9-CM. Results In multivariate models, women who reported napping daily were 44% more likely to die from any cause (95% confidence interval (CI) = 1.23–1.67), 58% more likely to die from cardiovascular causes (95% CI = 1.25–2.00), and 59% more likely to die from non-cardiovascular non-cancer causes (95% CI = 1.24–2.03) than women who did not nap daily. This relationship remained significant among relatively healthy women (those who reported no comorbidities). Compared to those who reported sleeeping 8–9 hours per 24 hours, women who slept 9–10 hours were at increased risk of death from cardiovascular and other (non-cardiovascular, non-cancer) causes. Conclusion Older women who reported napping daily or sleeping at least 9 hours per 24 hours are at increased risk of death from all causes except cancer. Future research could determine if specific sleep disorders contribute to these relationships. PMID:19220560

A Role for Histone Deacetylases in the Cellular and Behavioral Mechanisms Underlying Learning and Memory

ERIC Educational Resources Information Center

Mahgoub, Melissa; Monteggia, Lisa M.

2014-01-01

Histone deacetylases (HDACs) are a family of chromatin remodeling enzymes that restrict access of transcription factors to the DNA, thereby repressing gene expression. In contrast, histone acetyltransferases (HATs) relax the chromatin structure allowing for an active chromatin state and promoting gene transcription. Accumulating data have…

Nucleosome Recognition by the Piccolo NuA4 Histone Acetyltransferase Complex†

PubMed Central

Berndsen, Christopher E.; Selleck, William; McBryant, Steven J.; Hansen, Jeffrey C.; Tan, Song; Demi, John M.

2007-01-01

The mechanisms by which multisubunit histone acetyltransferase (HAT) complexes recognize and perform efficient acetylation on nucleosome substrates are largely unknown. Here, we use a variety of biochemical approaches and compare histone-based substrates of increasing complexity to determine the critical components of nucleosome recognition by the MOZ, Ybf2/Sas3, Sas2, Tip60 family HAT complex, Piccolo NuA4 (picNuA4). We find the histone tails to be dispensable for binding to both nucleosomes and free histones and that the H2A, H3, and H2B tails do not influence the ability of picNuA4 to tetra-acetylate the H4 tail within the nucleosome. Most notably, we discovered that the histone-fold domain (HFD) regions of histones, particularly residues 21–52 of H4, are critical for tight binding and efficient tail acetylation. Presented evidence suggests that picNuA4 recognizes the open surface of the nucleosome on which the HFD of H4 is located. This binding mechanism serves to direct substrate access to the tails of H4 and H2A and allows the enzyme to be “tethered”, thereby increasing the effective concentration of the histone tail and permitting successive cycles of H4 tail acetylation. PMID:17274630

O-GlcNAcylation of histone deacetylases 1 in hepatocellular carcinoma promotes cancer progression.

PubMed

Zhu, Guizhou; Tao, Tao; Zhang, Dongmei; Liu, Xiaojuan; Qiu, Huiyuan; Han, LiJian; Xu, Zhiwei; Xiao, Ying; Cheng, Chun; Shen, Aiguo

2016-08-01

Hepatocellular carcinoma (HCC) is a malignant tumor originating in the liver. Previous studies have indicated that O-GlcNAc transferase (OGT) and histone deacetylase-1 (HDAC1) play important roles in the pathogenesis of HCC. In the present study, we investigated the physical link between OGT and HDAC1. The O-GlcNAcylation of HDAC1 is overexpressed in HCC. We found that HDAC1 has two major sites of O-GlcNAcylation in its histone deacetylase domain. HDAC1 O-GlcNAcylation increases the activated phosphorylation of HDAC1, which enhances its enzyme activity. HDAC1 O-GlcNAc mutants promote the p21 transcription regulation through affecting the acetylation levels of histones from chromosome, and then influence the proliferation of HCC cells. We also found that mutants of O-GlcNAcylation site of HDAC1 affect invasion and migration of HepG2 cells. E-cadherin level is highly up-regulated in HDAC1 O-GlcNAc mutant-treated liver cancer cells, which inhibit the occurrence and development of HCC. Our findings suggest that OGT promotes the O-GlcNAc modification of HDAC1in the development of HCC. Therefore, inhibiting O-GlcNAcylation of HDAC1 may repress the progression of HCC. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Nicotine Suppressed Fetal Adrenal StAR Expression via YY1 Mediated-Histone Deacetylation Modification Mechanism.

PubMed

Liu, Lian; Wang, Jian-Fei; Fan, Jie; Rao, Yi-Song; Liu, Fang; Yan, You-E; Wang, Hui

2016-09-03

Steroidogenic acute regulatory (StAR) protein plays a pivotal role in steroidogenesis. Previously, we have demonstrated that prenatal nicotine exposure suppressed fetal adrenal steroidogenesis via steroidogenic factor 1 deacetylation. This study further explored the potential role of the transcriptional repressor Yin Yang 1 (YY1) in nicotine-mediated StAR inhibition. Nicotine was subcutaneously administered (1.0 mg/kg) to pregnant rats twice per day and NCI-H295A cells were treated with nicotine. StAR and YY1 expression were analyzed by real-time PCR, immunohistochemistry, and Western blotting. Histone modifications and the interactions between the YY1 and StAR promoter were assessed using chromatin immunoprecipitation (ChIP). Prenatal nicotine exposure increased YY1 expression and suppressed StAR expression. ChIP assay showed that there was a decreasing trend for histone acetylation at the StAR promoter in fetal adrenal glands, whereas H3 acetyl-K14 at the YY1 promoter presented an increasing trend following nicotine exposure. Furthermore, in nicotine-treated NCI-H295A cells, nicotine enhanced YY1 expression and inhibited StAR expression. ChIP assay showed that histone acetylation decreased at the StAR promoter in NCI-H295A cells and that the interaction between the YY1 and StAR promoter increased. These data indicated that YY1-medicated histone deacetylation modification in StAR promoters might play an important role in the inhibitory effect of nicotine on StAR expression.

Nicotine Suppressed Fetal Adrenal StAR Expression via YY1 Mediated-Histone Deacetylation Modification Mechanism

PubMed Central

Liu, Lian; Wang, Jian-Fei; Fan, Jie; Rao, Yi-Song; Liu, Fang; Yan, You-E; Wang, Hui

2016-01-01

Steroidogenic acute regulatory (StAR) protein plays a pivotal role in steroidogenesis. Previously, we have demonstrated that prenatal nicotine exposure suppressed fetal adrenal steroidogenesis via steroidogenic factor 1 deacetylation. This study further explored the potential role of the transcriptional repressor Yin Yang 1 (YY1) in nicotine-mediated StAR inhibition. Nicotine was subcutaneously administered (1.0 mg/kg) to pregnant rats twice per day and NCI-H295A cells were treated with nicotine. StAR and YY1 expression were analyzed by real-time PCR, immunohistochemistry, and Western blotting. Histone modifications and the interactions between the YY1 and StAR promoter were assessed using chromatin immunoprecipitation (ChIP). Prenatal nicotine exposure increased YY1 expression and suppressed StAR expression. ChIP assay showed that there was a decreasing trend for histone acetylation at the StAR promoter in fetal adrenal glands, whereas H3 acetyl-K14 at the YY1 promoter presented an increasing trend following nicotine exposure. Furthermore, in nicotine-treated NCI-H295A cells, nicotine enhanced YY1 expression and inhibited StAR expression. ChIP assay showed that histone acetylation decreased at the StAR promoter in NCI-H295A cells and that the interaction between the YY1 and StAR promoter increased. These data indicated that YY1-medicated histone deacetylation modification in StAR promoters might play an important role in the inhibitory effect of nicotine on StAR expression. PMID:27598153

Loss of the retinoblastoma binding protein 2 (RBP2) histone demethylase suppresses tumorigenesis in mice lacking Rb1 or Men1

PubMed Central

Lin, Wenchu; Cao, Jian; Liu, Jiayun; Beshiri, Michael L.; Fujiwara, Yuko; Francis, Joshua; Cherniack, Andrew D.; Geisen, Christoph; Blair, Lauren P.; Zou, Mike R.; Shen, Xiaohua; Kawamori, Dan; Liu, Zongzhi; Grisanzio, Chiara; Watanabe, Hideo; Minamishima, Yoji Andrew; Zhang, Qing; Kulkarni, Rohit N.; Signoretti, Sabina; Rodig, Scott J.; Bronson, Roderick T.; Orkin, Stuart H.; Tuck, David P.; Benevolenskaya, Elizaveta V.; Meyerson, Matthew; Kaelin, William G.; Yan, Qin

2011-01-01

Aberrations in epigenetic processes, such as histone methylation, can cause cancer. Retinoblastoma binding protein 2 (RBP2; also called JARID1A or KDM5A) can demethylate tri- and dimethylated lysine 4 in histone H3, which are epigenetic marks for transcriptionally active chromatin, whereas the multiple endocrine neoplasia type 1 (MEN1) tumor suppressor promotes H3K4 methylation. Previous studies suggested that inhibition of RBP2 contributed to tumor suppression by the retinoblastoma protein (pRB). Here, we show that genetic ablation of Rbp2 decreases tumor formation and prolongs survival in Rb1+/− mice and Men1-defective mice. These studies link RBP2 histone demethylase activity to tumorigenesis and nominate RBP2 as a potential target for cancer therapy. PMID:21788502

Daytime napping, sleep duration and serum C reactive protein: a population-based cohort study.

PubMed

Leng, Yue; Ahmadi-Abhari, Sara; Wainwright, Nick W J; Cappuccio, Francesco P; Surtees, Paul G; Luben, Robert; Brayne, Carol; Khaw, Kay-Tee

2014-11-11

To explore whether daytime napping and sleep duration are linked to serum C reactive protein (CRP), a pro-inflammatory marker, in an older aged British population. Cross-sectional study. European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk study. A total of 5018 men and women aged 48-92 years reported their sleep habits and had serum CRP levels measured. CRP was measured (mg/L) during 2006-2011 in fresh blood samples using high-sensitivity methods. Participants reported napping habits during 2002-2004, and reported sleep quantity during 2006-2007. Multivariable linear regression models were used to examine the association between napping and log-transformed CRP, and geometric mean CRP levels were calculated. After adjustment for age and sex, those who reported napping had 10% higher CRP levels compared with those not napping. The association was attenuated but remained borderline significant (β=0.05 (95% CI 0.00 to 0.10)) after further adjustment for social class, education, marital status, body mass index, physical activity, smoking, alcohol intake, self-reported health, pre-existing diseases, systolic blood pressure, hypnotic drug use, depression and in women-only hormone replacement therapy use. The geometric means (95% CI) of CRP levels were 2.38 (2.29 to 2.47) mg/L and 2.26 (2.21 to 2.32) mg/L for those who reported napping and no napping, respectively. A U-shaped association was observed between time spent in bed at night and CRP levels, and nighttime sleep duration was not associated with serum CRP levels. The association between napping and CRP was stronger for older participants, and among extremes of time spent in bed at night. Daytime napping was associated with increased CRP levels in an older aged British population. Further studies are needed to determine whether daytime napping is a cause for systemic inflammation, or if it is a symptom or consequence of underlying health problems. Published by the BMJ Publishing Group Limited

Multicenter Approach to Recurrent Acute and Chronic Pancreatitis in the United States: The North American Pancreatitis Study 2 (NAPS2)

PubMed Central

Whitcomb, David C.; Yadav, Dhiraj; Adam, Slivka; Hawes, Robert H.; Brand, Randall E.; Anderson, Michelle A.; Money, Mary E.; Banks, Peter A.; Bishop, Michele D.; Baillie, John; Sherman, Stuart; DiSario, James; Burton, Frank R.; Gardner, Timothy B.; Amann, Stephen T.; Gelrud, Andres; Lo, Simon K.; DeMeo, Mark T.; Steinberg, William M.; Kochman, Michael L.; Etemad, Babak; Forsmark, Christopher E.; Elinoff, Beth; Greer, Julia B.; O’Connell, Michael; Lamb, Janette; Barmada, M. Michael

2008-01-01

Background Recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) are complex syndromes associated with numerous etiologies, clinical variables and complications. We developed the North American Pancreatitis Study 2 (NAPS2) to be sufficiently powered to understand the complex environmental, metabolic and genetic mechanisms underlying RAP and CP. Methods Between August 2000 and September 2006, a consortium of 20 expert academic and private sites prospectively ascertained 1,000 human subjects with RAP or CP, plus 695 controls (spouse, family, friend or unrelated). Standardized questionnaires were completed by both the physicians and study subjects and blood was drawn for genomic DNA and biomarker studies. All data were double-entered into a database and systematically reviewed to minimize errors and include missing data. Results A total of 1,000 subjects (460 RAP, 540 CP) and 695 controls who completed consent forms and questionnaires and donated blood samples comprised the final dataset. Data were organized according to diagnosis, supporting documentation, etiological classification, clinical signs and symptoms (including pain patterns and duration, and quality of life), past medical history, family history, environmental exposures (including alcohol and tobacco use), medication use and therapeutic interventions. Upon achieving the target enrollment, data were organized and classified to facilitate future analysis. The approaches, rationale and datasets are described, along with final demographic results. Conclusion The NAPS2 consortium has successfully completed a prospective ascertainment of 1,000 subjects with RAP and CP from the USA. These data will be useful in elucidating the environmental, metabolic and genetic conditions, and to investigate the complex interactions that underlie RAP and CP. PMID:18765957

Erasers of Histone Acetylation: The Histone Deacetylase Enzymes

PubMed Central

Seto, Edward; Yoshida, Minoru

2014-01-01

Histone deacetylases (HDACs) are enzymes that catalyze the removal of acetyl functional groups from the lysine residues of both histone and nonhistone proteins. In humans, there are 18 HDAC enzymes that use either zinc- or NAD+-dependent mechanisms to deacetylate acetyl lysine substrates. Although removal of histone acetyl epigenetic modification by HDACs regulates chromatin structure and transcription, deacetylation of nonhistones controls diverse cellular processes. HDAC inhibitors are already known potential anticancer agents and show promise for the treatment of many diseases. PMID:24691964

Transrepressive function of TLX requires the histone demethylase LSD1.

PubMed

Yokoyama, Atsushi; Takezawa, Shinichiro; Schüle, Roland; Kitagawa, Hirochika; Kato, Shigeaki

2008-06-01

TLX is an orphan nuclear receptor (also called NR2E1) that regulates the expression of target genes by functioning as a constitutive transrepressor. The physiological significance of TLX in the cytodifferentiation of neural cells in the brain is known. However, the corepressors supporting the transrepressive function of TLX have yet to be identified. In this report, Y79 retinoblastoma cells were subjected to biochemical techniques to purify proteins that interact with TLX, and we identified LSD1 (also called KDM1), which appears to form a complex with CoREST and histone deacetylase 1. LSD1 interacted with TLX directly through its SWIRM and amine oxidase domains. LSD1 potentiated the transrepressive function of TLX through its histone demethylase activity as determined by a luciferase assay using a genomically integrated reporter gene. LSD1 and TLX were recruited to a TLX-binding site in the PTEN gene promoter, accompanied by the demethylation of H3K4me2 and deacetylation of H3. Knockdown of either TLX or LSD1 derepressed expression of the endogenous PTEN gene and inhibited cell proliferation of Y79 cells. Thus, the present study suggests that LSD1 is a prime corepressor for TLX.

Assessing the benefits of napping and short rest breaks on processing speed in sleep-restricted adolescents.

PubMed

Lim, Julian; Lo, June C; Chee, Michael W L

2017-04-01

Achievement-oriented adolescents often study long hours under conditions of chronic sleep restriction, adversely affecting cognitive function. Here, we studied how napping and rest breaks (interleaved off-task periods) might ameliorate the negative effects of sleep restriction on processing speed. Fifty-seven healthy adolescents (26 female, age = 15-19 years) participated in a 15-day live-in protocol. All participants underwent sleep restriction (5 h time-in-bed), but were then randomized into two groups: one of these groups received a daily 1-h nap opportunity. Data from seven of the study days (sleep restriction days 1-5, and recovery days 1-2) are reported here. The Blocked Symbol Decoding Test, administered once a day, was used to assess time-on-task effects and the effects of rest breaks on processing speed. Controlling for baseline differences, participants who took a nap demonstrated faster speed of processing and greater benefit across testing sessions from practice. These participants were also affected significantly less by time-on-task effects. In contrast, participants who did not receive a nap benefited more from the rest breaks that were permitted between blocks of the test. Our results indicate that napping partially reverses the detrimental effects of sleep restriction on processing speed. However, rest breaks have a greater effect as a countermeasure against poor performance when sleep pressure is higher. These data add to the growing body of evidence showing the importance of sleep for good cognitive functioning in adolescents, and suggest that more frequent rest breaks might be important in situations where sleep loss is unavoidable. © 2017 European Sleep Research Society.

Neighborhood socioeconomic status, sleep duration and napping in middle-to-old aged US men and women.

PubMed

Xiao, Qian; Hale, Lauren

2018-04-25

Earlier studies have linked neighborhood disadvantage with poor sleep outcomes. However, little is known about the association between changes in one's neighborhood over time and night sleep and napping. In over 300,000 middle-to-old aged Americans, we examined neighborhood socioeconomic status (SES) and change in neighborhood SES in relation to nocturnal sleep duration and napping. Nocturnal sleep duration and daytime napping were self-reported at baseline (1995-1996). Participants also reported baseline residential addresses, which were linked to US censuses. We derived a neighborhood SES index using census variables and calculated the baseline level and change (1990-2000) in neighborhood SES. Multinomial logistic regression was used to estimate the associations between neighborhood SES over time and nocturnal sleep and napping. Lower baseline neighborhood SES was associated short sleep, long sleep and napping. When compared with the highest quintile of neighborhood SES, the lowest was associated with 46% and 72% increase in relative risk (RR) of reporting very short (< 5 hours) sleep, 28% and 19% higher RR of long (≥9 hours) sleep and 95% and 85% increase in long (≥1 hours) nap in men and women, respectively. Moreover, a decrease in neighborhood SES was associated with higher RR of reporting very short sleep in women; while an improvement in neighborhood SES was associated with an increase in RR of long sleep in men. Neighborhood disadvantage and worsening neighborhood conditions were associated with unhealthy sleep behaviors. These results reinforce a growing literature on the potential importance of neighborhood context for understanding sleep health.

The role of a short post-lunch nap in improving cognitive, motor, and sprint performance in participants with partial sleep deprivation.

PubMed

Waterhouse, J; Atkinson, G; Edwards, B; Reilly, T

2007-12-01

The aim of this study was to determine the effects of a post-lunch nap on subjective alertness and performance following partial sleep loss. Ten healthy males (mean age 23.3 years, s = 3.4) either napped or sat quietly from 13:00 to 13:30 h after a night of shortened sleep (sleep 23:00-03:00 h only). Thirty minutes after the afternoon nap or control (no-nap) condition, alertness, short-term memory, intra-aural temperature, heart rate, choice reaction time, grip strength, and times for 2-m and 20-m sprints were recorded. The afternoon nap lowered heart rate and intra-aural temperature. Alertness, sleepiness, short-term memory, and accuracy at the 8-choice reaction time test were improved by napping (P < 0.05), but mean reaction times and grip strength were not affected (P > 0.05). Sprint times were improved. Mean time for the 2-m sprints fell from 1.060 s (s(x) = 0.018) to 1.019 s (s(x) = 0.019) (P = 0.031 paired t-test); mean time for the 20-m sprints fell from 3.971 s (s(x) = 0.054) to 3.878 s (s(x) = 0.047) (P = 0.013). These results indicate that a post-lunch nap improves alertness and aspects of mental and physical performance following partial sleep loss, and have implications for athletes with restricted sleep during training or before competition.

Nap-Dependent Learning in Infants

ERIC Educational Resources Information Center

Hupbach, Almut; Gomez, Rebecca L.; Bootzin, Richard R.; Nadel, Lynn

2009-01-01

Sleep has been shown to aid a variety of learning and memory processes in adults (Stickgold, 2005 ). Recently, we showed that infants' learning also benefits from subsequent sleep such that infants who nap are able to abstract the general grammatical pattern of a briefly presented artificial language (Gomez, Bootzin & Nadel, 2006 ). In the present…

Targeting histone deacetylases in endometrial cancer: a paradigm-shifting therapeutic strategy?

PubMed

Garmpis, N; Damaskos, C; Garmpi, A; Spartalis, E; Kalampokas, E; Kalampokas, T; Margonis, G-A; Schizas, D; Andreatos, N; Angelou, A; Lavaris, A; Athanasiou, A; Apostolou, K G; Spartalis, M; Damaskou, Z; Daskalopoulou, A; Diamantis, E; Tsivelekas, K; Alavanos, A; Valsami, S; Moschos, M M; Sampani, A; Nonni, A; Antoniou, E A; Mantas, D; Tsourouflis, G; Markatos, K; Kontzoglou, K; Perrea, D; Nikiteas, N; Kostakis, A; Dimitroulis, D

2018-02-01

Endometrial cancer is increasingly prevalent in western societies and affects mainly postmenopausal women; notably incidence rates have been rising by 1.9% per year on average since 2005. Although the early-stage endometrial cancer can be effectively managed with surgery, more advanced stages of the disease require multimodality treatment with varying results. In recent years, endometrial cancer has been extensively studied at the molecular level in an attempt to develop effective therapies. Recently, a family of compounds that alter epigenetic expression, namely histone deacetylase inhibitors, have shown promise as possible therapeutic agents in endometrial cancer. The present review aims to discuss the therapeutic potential of these agents. This literature review was performed using the MEDLINE database; the search terms histone, deacetylase, inhibitors, endometrial, targeted therapies for endometrial cancer were employed to identify relevant studies. We only reviewed English language publications and also considered studies that were not entirely focused on endometrial cancer. Ultimately, sixty-four articles published until January 2018 were incorporated into our review. Studies in cell cultures have demonstrated that histone deacetylase inhibitors exert their antineoplastic activity by promoting expression of p21WAF1 and p27KIP1, cyclin-dependent kinase inhibitors, that have important roles in cell cycle regulation; importantly, the transcription of specific genes (e.g., E-cadherin, PTEN) that are commonly silenced in endometrial cancer is also enhanced. In addition to these abstracts effects, novel compounds with histone deacetylase inhibitor activity (e.g., scriptaid, trichostatin, entinostat) have also demonstrated significant antineoplastic activity both in vitro and in vivo, by liming tumor growth, inducing apoptosis, inhibiting angiogenesis and potentiating the effects of chemotherapy. The applications of histone deacetylase inhibitors in endometrial

The Effects of an Afternoon Nap on Episodic Memory in Young and Older Adults

PubMed Central

Fairley, Jacqueline; Decker, Michael J.; Bliwise, Donald L.

2017-01-01

Abstract Study Objectives: In young adults, napping is hypothesized to benefit episodic memory retention (eg, via consolidation). Whether this relationship is present in older adults has not been adequately tested but is an important question because older adults display marked changes in sleep and memory. Design: Between-subjects design. Setting: Sleep laboratory at Emory University School of Medicine. Participants: Fifty healthy young adults (18–29) and 45 community-dwelling older adults (58–83). Intervention: Participants were randomly assigned to a 90-minute nap opportunity or an equal interval of quiet wakefulness. Measurements and Results: Participants underwent an item-wise directed forgetting learning procedure in which they studied words that were individually followed by the instruction to “remember” or “forget.” Following a 90-minute retention interval filled with quiet wakefulness or a nap opportunity, they were asked to free recall and recognize those words. Young adults retained significantly more words following a nap interval than a quiet wakefulness interval on both free recall and recognition tests. There was modest evidence for greater nap-related retention of “remember” items relative to “forget” items for free recall but not recognition. Older adults’ memory retention did not differ across nap and quiet wakefulness conditions, although they demonstrated greater fragmentation, lower N3, and lower rapid eye movement duration than the young adults. Conclusions: In young adults, an afternoon nap benefits episodic memory retention, but such benefits decrease with advancing age. PMID:28329381

The interactive effects of nocturnal sleep and daytime naps in relation to serum C-reactive protein.

PubMed

Mantua, Janna; Spencer, Rebecca M C

2015-10-01

C-reactive protein (CRP) is a general marker of inflammation that has been differentially linked with sleep. Elevated CRP (ie, high inflammation) has been associated with either short/insufficient sleep duration or long sleep duration, both, or neither. Daytime napping has also been tied to increased and decreased inflammation. We attempted to unify these findings by examining the relationship between CRP and sleep duration in conjunction with napping in a healthy young adult cohort. Participants were young adults (mean age = 29.05 years, n = 2147) from the National Longitudinal Study of Adolescent Health (Add Health) cohort, a nationally representative longitudinal sample. Analysis of covariance (ANCOVA) tests examined whether self-reported sleep duration (short, medium, or long) and nap frequency (none-few days/week; most days/week; every day) interacted in relation to CRP. Standard covariates (ie, age, gender, race/ethnicity, body mass index, physical activity, depression, snoring, systolic blood pressure, clinical symptoms, and household income) were used. There was a linear increase in CRP with increased napping [contrast estimate = 0.265, 95% confidence interval (CI) (0.045-0.485), P = 0.018]. There was also an interaction between sleep duration and napping frequency in relation to CRP (F4,2128 = 2.90, P = 0.021). Inflammation differed between nap groups within the long and short sleep groups. Our results suggest that increased napping is an independent predictor of inflammation in young adults. These results also provide evidence for interactive effects of inflammation, nocturnal sleep, and daytime naps. Our findings confirm that excess sleep, insufficient sleep, frequent napping, and infrequent napping can all be linked with elevated CRP, but these relationships depend on both nocturnal and daytime sleep patterns. These analyses will guide future work to more specifically examine sleep-inflammation processes and directionality

Effects of a 20-Min Nap Post Normal and Jet Lag Conditions on P300 Components in Athletes.

PubMed

Petit, Elisabeth; Bourdin, Hubert; Tio, Grégory; Yenil, Omer; Haffen, Emmanuel; Mougin, Fabienne

2018-05-14

Post-lunch sleepiness belongs to biological rhythms. Athletes take a nap to counteract afternoon circadian nadir, in prevision of disturbed sleep. This study examined the effects of brief post-lunch nap on vigilance in young and healthy athletes. The P300 components, physiological and cognitive performances were assessed either after nap or rest, following a night of normal sleep (NSC) or simulated jet lag condition (5-h advance-JLC). P300 wave is the positive deflection at about 300 ms in response to a rare stimulus, representing higher information processing. P300 amplitude reflects the amount of attention allocated whereas P300 latency reflects time spent on stimulus classification. P300 amplitude was significantly increased (Fz:11.14±3.0vs9.05±3.2 µV; p<0.05) and P300 latency was shorter (Pz:327.16±18.0vs344.90±17.0 ms; p<0.01) after nap in NSC. These changes were accompanied by lower subjective sleepiness (19.7±9.6vs27.5±16.5; p<0.05) and decrease in mean reaction times (MRT: divided attention, 645.1±74.2vs698±80.4 ms; p<0.05). In contrast, in JLC, only P300 amplitudes (Fz:10.30±3.1vs7.54±3.3 µV; p<0.01 and Cz: 11.48±3.1vs9.77±3.6 µV; p<0.05) increased but P300 latencies or MRT did not improve. These results indicated improvements in speed of stimulus evaluation time. Napping positively impacts on cognitive processing, especially when subjects are on normal sleep schedules. A nap should be planned for athletes whose performance requires speedy and accurate decisions. © Georg Thieme Verlag KG Stuttgart · New York.

The histone chaperone ASF1 is essential for sexual development in the filamentous fungus Sordaria macrospora.

PubMed

Gesing, Stefan; Schindler, Daniel; Fränzel, Benjamin; Wolters, Dirk; Nowrousian, Minou

2012-05-01

Ascomycetes develop four major types of fruiting bodies that share a common ancestor, and a set of common core genes most likely controls this process. One way to identify such genes is to search for conserved expression patterns. We analysed microarray data of Fusarium graminearum and Sordaria macrospora, identifying 78 genes with similar expression patterns during fruiting body development. One of these genes was asf1 (anti-silencing function 1), encoding a predicted histone chaperone. asf1 expression is also upregulated during development in the distantly related ascomycete Pyronema confluens. To test whether asf1 plays a role in fungal development, we generated an S. macrospora asf1 deletion mutant. The mutant is sterile and can be complemented to fertility by transformation with the wild-type asf1 and its P. confluens homologue. An ASF1-EGFP fusion protein localizes to the nucleus. By tandem-affinity purification/mass spectrometry as well as yeast two-hybrid analysis, we identified histones H3 and H4 as ASF1 interaction partners. Several developmental genes are dependent on asf1 for correct transcriptional expression. Deletion of the histone chaperone genes rtt106 and cac2 did not cause any developmental phenotypes. These data indicate that asf1 of S. macrospora encodes a conserved histone chaperone that is required for fruiting body development. © 2012 Blackwell Publishing Ltd.

The chaperone-histone partnership: for the greater good of histone traffic and chromatin plasticity.

PubMed

Hondele, Maria; Ladurner, Andreas G

2011-12-01

Histones are highly positively charged proteins that wrap our genome. Their surface properties also make them prone to nonspecific interactions and aggregation. A class of proteins known as histone chaperones is dedicated to safeguard histones by aiding their proper incorporation into nucleosomes. Histone chaperones facilitate ordered nucleosome assembly and disassembly reactions through the formation of semi-stable histone-chaperone intermediates without requiring ATP, but merely providing a complementary protein surface for histones to dynamically interact with. Recurrent 'chaperoning' mechanisms involve the masking of the histone's positive charge and the direct blocking of crucial histone surface sites, including those required for H3-H4 tetramerization or the binding of nucleosomal DNA. This shielding prevents histones from engaging in premature or unwanted interactions with nucleic acids and other cellular components. In this review, we analyze recent structural studies on chaperone-histone interactions and discuss the implications of this vital partnership for nucleosome assembly and disassembly pathways. Copyright © 2011 Elsevier Ltd. All rights reserved.

Crystal structures of fission yeast histone chaperone Asf1 complexed with the Hip1 B-domain or the Cac2 C terminus.

PubMed

Malay, Ali D; Umehara, Takashi; Matsubara-Malay, Kazuko; Padmanabhan, Balasundaram; Yokoyama, Shigeyuki

2008-05-16

The assembly of core histones onto eukaryotic DNA is modulated by several histone chaperone complexes, including Asf1, CAF-1, and HIRA. Asf1 is a unique histone chaperone that participates in both the replication-dependent and replication-independent pathways. Here we report the crystal structures of the apo-form of fission yeast Asf1/Cia1 (SpAsf1N; residues 1-161) as well as its complexes with the B-domain of the fission yeast HIRA orthologue Hip1 (Hip1B) and the C-terminal region of the Cac2 subunit of CAF-1 (Cac2C). The mode of the fission yeast Asf1N-Hip1B recognition is similar to that of the human Asf1-HIRA recognition, suggesting that Asf1N recognition of Hip1B/HIRA is conserved from yeast to mammals. Interestingly, Hip1B and Cac2C show remarkably similar interaction modes with Asf1. The binding between Asf1N and Hip1B was almost completely abolished by the D37A and L60A/V62A mutations in Asf1N, indicating the critical role of salt bridge and van der Waals contacts in the complex formation. Consistently, both of the aforementioned Asf1 mutations also drastically reduced the binding to Cac2C. These results provide a structural basis for a mutually exclusive Asf1-binding model of CAF-1 and HIRA/Hip1, in which Asf1 and CAF-1 assemble histones H3/H4 (H3.1/H4 in vertebrates) in a replication-dependent pathway, whereas Asf1 and HIRA/Hip1 assemble histones H3/H4 (H3.3/H4 in vertebrates) in a replication-independent pathway.

STED nanoscopy of the centrosome linker reveals a CEP68-organized, periodic rootletin network anchored to a C-Nap1 ring at centrioles.

PubMed

Vlijm, Rifka; Li, Xue; Panic, Marko; Rüthnick, Diana; Hata, Shoji; Herrmannsdörfer, Frank; Kuner, Thomas; Heilemann, Mike; Engelhardt, Johann; Hell, Stefan W; Schiebel, Elmar

2018-03-06

The centrosome linker proteins C-Nap1, rootletin, and CEP68 connect the two centrosomes of a cell during interphase into one microtubule-organizing center. This coupling is important for cell migration, cilia formation, and timing of mitotic spindle formation. Very little is known about the structure of the centrosome linker. Here, we used stimulated emission depletion (STED) microscopy to show that each C-Nap1 ring at the proximal end of the two centrioles organizes a rootletin ring and, in addition, multiple rootletin/CEP68 fibers. Rootletin/CEP68 fibers originating from the two centrosomes form a web-like, interdigitating network, explaining the flexible nature of the centrosome linker. The rootletin/CEP68 filaments are repetitive and highly ordered. Staggered rootletin molecules (N-to-N and C-to-C) within the filaments are 75 nm apart. Rootletin binds CEP68 via its C-terminal spectrin repeat-containing region in 75-nm intervals. The N-to-C distance of two rootletin molecules is ∼35 to 40 nm, leading to an estimated minimal rootletin length of ∼110 nm. CEP68 is important in forming rootletin filaments that branch off centrioles and to modulate the thickness of rootletin fibers. Thus, the centrosome linker consists of a vast network of repeating rootletin units with C-Nap1 as ring organizer and CEP68 as filament modulator. Copyright © 2018 the Author(s). Published by PNAS.