Role of erythroid Kruppel-like factor in human γ- to β-globin gene switching

Erythroid Kruppel-like factor (EKLF) is an erythroid-specific transcription factor that contains zinc finger domains similar to the Kruppel protein of Drosophila melanogaster. Previous studies demonstrated that EKLF binds to the CACCC box in the human β-globin gene promoter and activates transcription. CACCC box mutations that cause severe β-thalassemias in humans inhibit EKLF binding. Results described in this paper suggest that EKLF functions predominately in adult erythroid tissue. The EKLF gene is expressed at a 3-fold higher level in adult erythroid tissue than in fetal erythroid tissue, and the EKLF protein binds to the human β-globin promoter 8-fold more efficiently than to the human γ-globin promoter. Co-transfection experiments in the human fetal-like erythroleukemia cell line K562 demonstrate that over-expression of EKLF activates a β-globin reporter construct 1000-fold; a linked γ-globin reporter is activated only 3-fold. Mutation of the β-globin CACCC box severely inhibits activation. These results demonstrate that EKLF is a developmental stage-enriched protein that preferentially activates human β-globin gene expression. The data strongly suggest that EKLF is an important factor involved in human γ- to β-globin gene switching

Effects of Interventions Addressing School Environments or Educational Assets on Adolescent Sexual Health: Systematic Review and Meta-analysis.

CONTEXT: School-based interventions that aim to modify sexual health knowledge, attitudes and behaviors have mixed and often unsustained effects on adolescent sexual health outcomes. However, observational evidence suggests that broader school-related factors, such as school climate and academic attainment, can influence outcomes. METHODS: Nine databases were searched in July 2017 for randomized and quasi-experimental evaluations of interventions addressing school-level environment or student-level educational assets, to examine whether such interventions can promote young people's sexual health. Searches were limited to studies published since 1990 but were not restricted by language. Studies were assessed for risk of bias and synthesized narratively and meta-analytically. RESULTS: Searches yielded 11 evaluations, published from 1999 to 2016, of interventions related to school-level environment or student-level educational assets. Because of inconsistent reporting, the risk of bias was not clear for most studies, and meta-analysis was possible for only one outcome. The meta-analysis of three randomized trials provided some evidence that school-environment interventions may delay sexual debut (pooled odds ratio, 0.5). Narrative synthesis of the remaining outcomes found mixed results, but suggests that interventions addressing school-level environment may delay sexual debut and that those addressing student-level educational assets may reduce risk of pregnancy and STDs. CONCLUSIONS: Additional and more rigorous evidence is needed to assess the probability that interventions addressing school-related factors are effective and to provide better understanding of the mechanisms by which they may work to improve adolescent sexual health

Determinants of smoking and cessation in older women

BACKGROUND: although the benefits of quitting smoking even at an advanced age have been proved, few campaigns target the older population. The goals of this study were to analyse the characteristics of older women smokers help and support those wanting to quit. METHODS: we assessed the determinants of smoking cessation in a prospective cohort study performed in 7,609 older women. A questionnaire about smoking habits was sent to the 486 eligible smokers. Smoking dependence and smokers' readiness to quit was assessed. Participants who had quit smoking during follow-up were asked about their previous reasons for quitting and the methods used to quit. RESULTS: 372 women of the 424 (88%) responded to our questionnaire and were included. The most common reasons for smoking were relaxation, pleasure, and habit. Major obstacles to quitting smoking were 'no benefit to quitting at an advanced age', 'smoking few or "light" cigarettes yields no negative health consequences', and 'smoking does not increase osteoporotic risk'. During the 3-year follow-up period, 57 of the 372 (15%) women successfully quit smoking. Being an occasional smoker (OR=2.4) and reporting 'quitting is not difficult' (OR=3.7) were positively associated with having recently quit smoking. Only 11% of successful cessations were reported to have received physician advice. CONCLUSIONS: these data illustrate the specific smoking behaviour of older women, suggesting that cessation interventions ought to be tailored to these characteristics. Willingness to quit was associated with a low education level. The most frequent obstacles to quitting were all based on incorrect information

Multiple elements in human β-globin locus control region 5′ HS 2 are involved in enhancer activity and position independent, transgene expression

The human β-globin Locus Control Region (LCR) has two important activities. First, the LCR opens a 200 kb chromosomal domain containing the human ε-, γ- and β-giobin genes and, secondly, these sequences function as a powerful enhancer of ε-, γ- and β-globin gene expression. Erythrold-specific, DNase I hypersensitive sites (HS) mark sequences that are critical for LCR activity. Previous experiments demonstrated that a 1.9 kb fragment containing the 5′ HS 2 site confers position-independent expression in transgenic mice and enhances human β-giobin gene expression 100-fold. Further analysis of this region demonstrates that multiple sequences are required for maximal enhancer activity; deletion of SP1, NF-E2, GATA-1 or USF binding sites significantly decrease β-globin gene expression. In contrast, no single site is required for position- independent transgene expression; all mice with site- specific mutations in 5′ HS 2 express human β-globin mRNA regardless of the site of transgene integration. Apparently, multiple combinations of protein binding sites in 5′ HS 2 are sufficient to prevent chromosomal position effects that inhibit transgene expression. © 1994 Oxford University Press

Atividade de peroxidase de três populações de "Switchgrass" (Panicum virgatum L.) em resposta à injúria do pulgão-verdedos-cereais (Schizaphis graminum) (Hemiptera: Aphididae).

?Switchgrass? é uma gramínea que tem recebido atenção especial como uma cultura bioenergética nos EUA. Os pulgões foram relatados como uma praga potencial em populações desta gramínea e não está claro como a manipulação genética para uma melhor produção de bioenergia afetará a capacidade da planta em tolerar a injuria deste inseto. Portanto, os objetivos deste estudo foram comparar o teor de proteína total e atividade de peroxidase de três populações de ?switchgrass? (Kanlow, KxS e Summer) a injuria pelo pulgão-verde-dos-cereais

Epigenetic Chromatin Silencing: Bistability and Front Propagation

The role of post-translational modification of histones in eukaryotic gene regulation is well recognized. Epigenetic silencing of genes via heritable chromatin modifications plays a major role in cell fate specification in higher organisms. We formulate a coarse-grained model of chromatin silencing in yeast and study the conditions under which the system becomes bistable, allowing for different epigenetic states. We also study the dynamics of the boundary between the two locally stable states of chromatin: silenced and unsilenced. The model could be of use in guiding the discussion on chromatin silencing in general. In the context of silencing in budding yeast, it helps us understand the phenotype of various mutants, some of which may be non-trivial to see without the help of a mathematical model. One such example is a mutation that reduces the rate of background acetylation of particular histone side-chains that competes with the deacetylation by Sir2p. The resulting negative feedback due to a Sir protein depletion effect gives rise to interesting counter-intuitive consequences. Our mathematical analysis brings forth the different dynamical behaviors possible within the same molecular model and guides the formulation of more refined hypotheses that could be addressed experimentally.Comment: 19 pages, 5 figure

LEARNING AND VISUALIZING MUSIC SPECIFICATIONS USING PATTERN GRAPHS

ABSTRACT We describe a system to learn and visualize specifications from song(s) in symbolic and audio formats. The core of our approach is based on a software engineering procedure called specification mining. Our procedure extracts patterns from feature vectors and uses them to build pattern graphs. The feature vectors are created by segmenting song(s) and extracting time and and frequency domain features from them, such as chromagrams, chord degree and interval classification. The pattern graphs built on these feature vectors provide the likelihood of a pattern between nodes, as well as start and ending nodes. The pattern graphs learned from a song(s) describe formal specifications that can be used for human interpretable quantitatively and qualitatively song comparison or to perform supervisory control in machine improvisation. We offer results in song summarization, song and style validation and machine improvisation with formal specifications

Transcriptional analysis of defense mechanisms in upland tetraploid switchgrass to greenbugs

Background: Aphid infestation of switchgrass (Panicum virgatum) has the potential to reduce yields and biomass quality. Although switchgrass-greenbug (Schizaphis graminum; GB) interactions have been studied at the whole plant level, little information is available on plant defense responses at the molecular level. Results: The global transcriptomic response of switchgrass cv Summer to GB was monitored by RNA-Seq in infested and control (uninfested) plants harvested at 5, 10, and 15 days after infestation (DAI). Differentially expressed genes (DEGs) in infested plants were analyzed relative to control uninfested plants at each time point. DEGs in GB-infested plants induced by 5-DAI included an upregulation of reactive burst oxidases and several cell wall receptors. Expression changes in genes linked to redox metabolism, cell wall structure, and hormone biosynthesis were also observed by 5- DAI. At 10-DAI, network analysis indicated a massive upregulation of defense-associated genes, including NAC, WRKY, and MYB classes of transcription factors and potential ancillary signaling molecules such as leucine aminopeptidases. Molecular evidence for loss of chloroplastic functions was also detected at this time point. Supporting these molecular changes, chlorophyll content was significantly decreased, and ROS levels were elevated in infested plants 10-DAI. Total peroxidase and laccase activities were elevated in infested plants at 10-DAI relative to control uninfested plants. The net result appeared to be a broad scale defensive response that led to an apparent reduction in C and N assimilation and a potential redirection of nutrients away from GB and towards the production of defensive compounds, such as pipecolic acid, chlorogenic acid, and trehalose by 10-DAI. By 15-DAI, evidence of recovery in primary metabolism was noted based on transcript abundances for genes associated with carbon, nitrogen, and nutrient assimilation. Conclusions: Extensive remodeling of the plant transcriptome and the production of ROS and several defensive metabolites in an upland switchgrass cultivar were observed in response to GB feeding. The early loss and apparent recovery in primary metabolism by 15-DAI would suggest that these transcriptional changes in later stages of GB infestation could underlie the recovery response categorized for this switchgrass cultivar. These results can be exploited to develop switchgrass lines with more durable resistance to GB and potentially other aphids