Study of the Epigenetic Signals in the Human Genome

Epigenetics can be defined as changes in the genome that are inherited during cell division, but without direct modification of the DNA sequence. These genomic changes are supported by three major epigenetic mechanisms: DNA methylation, histone modification and small RNAs. Different epigenetic marks function regulate gene transcription, some of them when altered can trigger various diseases such as cancer. This work is focus on the epigenetic signals in the human genome, studding the dependency between the nucleotide word context and the occurrence of epigenomic marking. We based our study on histone epigenomes available in the NIH Roadmap Epigenomics Mapping Consortium database that contains various types of cells and various types of tissues. We compared genomic contexts of epigenetic marking among chromosomes and among epigenomes. We included a control scenario, the DNA sequence regions without epigenetic marking. We identified significant differences between context occurrence of control and epigenetic regions. The genomic words in epigenetic marking regions present significant association with chromosome and histone modification type

Age-related differences in adaptation during childhood: The influences of muscular power production and segmental energy flow caused by muscles

Acquisition of skillfulness is not only characterized by a task-appropriate application of muscular forces but also by the ability to adapt performance to changing task demands. Previous research suggests that there is a different developmental schedule for adaptation at the kinematic compared to the neuro-muscular level. The purpose of this study was to determine how age-related differences in neuro-muscular organization affect the mechanical construction of pedaling at different levels of the task. By quantifying the flow of segmental energy caused by muscles, we determined the muscular synergies that construct the movement outcome across movement speeds. Younger children (5-7 years; n = 11), older children (8-10 years; n = 8), and adults (22-31 years; n = 8) rode a stationary ergometer at five discrete cadences (60, 75, 90, 105, and 120 rpm) at 10% of their individually predicted peak power output. Using a forward dynamics simulation, we determined the muscular contributions to crank power, as well as muscular power delivered to the crank directly and indirectly (through energy absorption and transfer) during the downstroke and the upstroke of the crank cycle. We found significant age × cadence interactions for (1) peak muscular power at the hip joint [Wilks' Lambda = 0.441, F(8,42) = 2.65, p = 0.019] indicating that at high movement speeds children produced less peak power at the hip than adults, (2) muscular power delivered to the crank during the downstroke and the upstroke of the crank cycle [Wilks' Lambda = 0.399, F(8,42) = 3.07, p = 0.009] indicating that children delivered a greater proportion of the power to the crank during the upstroke when compared to adults, (3) hip power contribution to limb power [Wilks' Lambda = 0.454, F(8,42) = 2.54, p = 0.023] indicating a cadence-dependence of age-related differences in the muscular synergy between hip extensors and plantarflexors. The results demonstrate that in spite of a successful performance, children construct the task of pedaling differently when compared to adults, especially when they are pushed to their performance limits. The weaker synergy between hip extensors and plantarflexors suggests that a lack of inter-muscular coordination, rather than muscular power production per se, is a factor that limits children's performance ranges

Education and transfer of water competencies: An ecological dynamics approach

© The Author(s) 2020. To cope in various aquatic environments (i.e. swimming pools, lakes, rivers, oceans), learners require a wide repertoire of self-regulatory behaviours such as awareness of obstacles and water properties, floating and moving from point to point with different strokes, decision making, emotional control and breathing efficiently. By experiencing different learning situations in stable indoor pool environments, it is assumed that children strengthen aquatic competencies that should be transferable to functioning in open water environments, where prevalence of drowning is high. However, this fundamental assumption may be misleading. Here, we propose the application of a clear, related methodology and theoretical framework that could be useful to help physical education curriculum specialists (re)shape and (re)design appropriate aquatic learning situations to facilitate better transfer of learning. We discuss the need for more representativeness in a learning environment, proposing how the many different task and environmental constraints on aquatic actions may bound the emergence of functional, self-regulatory behaviours in learners. Ideas in ecological dynamics suggest that physical educators should design learning environments that offer a rich landscape of opportunities for action for learners. As illustration, three practice interventions are described for developing functional and transferrable skills in indoor aquatic environments. It is important that aquatic educators focus not just upon ‘learning to swim’, but particularly on relevant transferable skills and self-regulatory behaviours deemed necessary for functioning in dynamic, outdoor aquatic environments

Education and transfer of water competencies: An ecological dynamics approach

© The Author(s) 2020. To cope in various aquatic environments (i.e. swimming pools, lakes, rivers, oceans), learners require a wide repertoire of self-regulatory behaviours such as awareness of obstacles and water properties, floating and moving from point to point with different strokes, decision making, emotional control and breathing efficiently. By experiencing different learning situations in stable indoor pool environments, it is assumed that children strengthen aquatic competencies that should be transferable to functioning in open water environments, where prevalence of drowning is high. However, this fundamental assumption may be misleading. Here, we propose the application of a clear, related methodology and theoretical framework that could be useful to help physical education curriculum specialists (re)shape and (re)design appropriate aquatic learning situations to facilitate better transfer of learning. We discuss the need for more representativeness in a learning environment, proposing how the many different task and environmental constraints on aquatic actions may bound the emergence of functional, self-regulatory behaviours in learners. Ideas in ecological dynamics suggest that physical educators should design learning environments that offer a rich landscape of opportunities for action for learners. As illustration, three practice interventions are described for developing functional and transferrable skills in indoor aquatic environments. It is important that aquatic educators focus not just upon ‘learning to swim’, but particularly on relevant transferable skills and self-regulatory behaviours deemed necessary for functioning in dynamic, outdoor aquatic environments

Ethnic differences in ovulatory function in nulliparous women

African-American women have a long-standing approximately 20% higher breast cancer incidence rate than USA White women under age 40 while rates among Latinas are lower than those of Whites. The reasons for this are not clear, however they may be due to ethnic differences in circulating oestradiol and progesterone levels. In a cross-sectional study, we investigated whether anovulation frequency and circulating serum oestradiol and/or progesterone levels vary among normally cycling nulliparous African-American (n=60), Latina (n=112) and non-Latina White (n=69) women. Blood and urine specimens were collected over two menstrual cycles among healthy 17- to 34-year-old women. Frequency of anovulation was greater among White women (nine out of 63, 14.3%) than African-American women (four out of 56, 7.1%) or Latina women (seven out of 102, 6.9%), although these differences were not statistically significant. African-American women had 9.9% (P=0.26) higher follicular phase oestradiol concentrations than Latina women and 17.4% (P=0.13) higher levels than White women. African-American women also had considerably higher levels of luteal phase oestradiol (vs Latinas, +9.4%, P=0.14; vs Whites, +25.3%, P=0.003) and progesterone (vs Latinas, +15.4%, P=0.07; vs Whites, +36.4%, P=0.002). Latina women were also observed to have higher follicular oestradiol, and luteal oestradiol and progesterone levels than White women (follicular oestradiol: +6.8%, P=0.48; luteal oestradiol: +14.6%, P=0.04; luteal progesterone: +18.2%, P=0.06). These results suggest that exposure to endogenous steroid hormones may be greater for young African-American and Latina women than for Whites

On the Integrand-Reduction Method for Two-Loop Scattering Amplitudes

We propose a first implementation of the integrand-reduction method for two-loop scattering amplitudes. We show that the residues of the amplitudes on multi-particle cuts are polynomials in the irreducible scalar products involving the loop momenta, and that the reduction of the amplitudes in terms of master integrals can be realized through polynomial fitting of the integrand, without any apriori knowledge of the integral basis. We discuss how the polynomial shapes of the residues determine the basis of master integrals appearing in the final result. We present a four-dimensional constructive algorithm that we apply to planar and non-planar contributions to the 4- and 5-point MHV amplitudes in N=4 SYM. The technique hereby discussed extends the well-established analogous method holding for one-loop amplitudes, and can be considered a preliminary study towards the systematic reduction at the integrand-level of two-loop amplitudes in any gauge theory, suitable for their automated semianalytic evaluation.Comment: 26 pages, 11 figure

Macular and serum carotenoid concentrations in patients with malabsorption syndromes

The carotenoids lutein and zeaxanthin are believed to protect the human macula by absorbing blue light and quenching free radicals. Intestinal malabsorption syndromes such as celiac and Crohn’s disease are known to cause deficiencies of lipid-soluble nutrients. We hypothesized that subjects with nutrient malabsorption syndromes will demonstrate lower carotenoid levels in the macula and blood, and that these lower levels may correlate with early-onset maculopathy. Resonance Raman spectrographic (RRS) measurements of macular carotenoid levels were collected from subjects with and without a history of malabsorption syndromes. Carotenoids were extracted from serum and analyzed by high performance liquid chromatography (HPLC). Subjects with malabsorption (n = 22) had 37% lower levels of macular carotenoids on average versus controls (n = 25, P < 0.001). Malabsorption was not associated with decreased serum carotenoid levels. Convincing signs of early maculopathy were not observed. We conclude that intestinal malabsorption results in lower macular carotenoid levels

Complex exon-intron marking by histone modifications is not determined solely by nucleosome distribution

It has recently been shown that nucleosome distribution, histone modifications and RNA polymerase II (Pol II) occupancy show preferential association with exons (“exon-intron marking”), linking chromatin structure and function to co-transcriptional splicing in a variety of eukaryotes. Previous ChIP-sequencing studies suggested that these marking patterns reflect the nucleosomal landscape. By analyzing ChIP-chip datasets across the human genome in three cell types, we have found that this marking system is far more complex than previously observed. We show here that a range of histone modifications and Pol II are preferentially associated with exons. However, there is noticeable cell-type specificity in the degree of exon marking by histone modifications and, surprisingly, this is also reflected in some histone modifications patterns showing biases towards introns. Exon-intron marking is laid down in the absence of transcription on silent genes, with some marking biases changing or becoming reversed for genes expressed at different levels. Furthermore, the relationship of this marking system with splicing is not simple, with only some histone modifications reflecting exon usage/inclusion, while others mirror patterns of exon exclusion. By examining nucleosomal distributions in all three cell types, we demonstrate that these histone modification patterns cannot solely be accounted for by differences in nucleosome levels between exons and introns. In addition, because of inherent differences between ChIP-chip array and ChIP-sequencing approaches, these platforms report different nucleosome distribution patterns across the human genome. Our findings confound existing views and point to active cellular mechanisms which dynamically regulate histone modification levels and account for exon-intron marking. We believe that these histone modification patterns provide links between chromatin accessibility, Pol II movement and co-transcriptional splicing

SARS and hospital priority setting: a qualitative case study and evaluation

BACKGROUND: Priority setting is one of the most difficult issues facing hospitals because of funding restrictions and changing patient need. A deadly communicable disease outbreak, such as the Severe Acute Respiratory Syndrome (SARS) in Toronto in 2003, amplifies the difficulties of hospital priority setting. The purpose of this study is to describe and evaluate priority setting in a hospital in response to SARS using the ethical framework 'accountability for reasonableness'. METHODS: This study was conducted at a large tertiary hospital in Toronto, Canada. There were two data sources: 1) over 200 key documents (e.g. emails, bulletins), and 2) 35 interviews with key informants. Analysis used a modified thematic technique in three phases: open coding, axial coding, and evaluation. RESULTS: Participants described the types of priority setting decisions, the decision making process and the reasoning used. Although the hospital leadership made an effort to meet the conditions of 'accountability for reasonableness', they acknowledged that the decision making was not ideal. We described good practices and opportunities for improvement. CONCLUSIONS: 'Accountability for reasonableness' is a framework that can be used to guide fair priority setting in health care organizations, such as hospitals. In the midst of a crisis such as SARS where guidance is incomplete, consequences uncertain, and information constantly changing, where hour-by-hour decisions involve life and death, fairness is more important rather than less

Environmental Conditions Influence Allometric Patterns in the Blow Fly, Chrysomya albiceps

The objective of this research was to study variations in allometry of body characters in females and males of two populations of blow flies, Chrysomya albiceps (Wiedemann) (Diptera: Calliphoridae), under different environmental conditions to establish patterns of morphological variation. Body size of both males and females in the experimental population was significantly higher than in the individuals of the natural population, indicating an important influence of food on body size. All genitalic and non-genitalic characters in males and females of the two populations showed a trend towards negative allometry rather than isometry. Allometric patterns were modified in both sexes and between populations. The data show generally larger allometric slopes in females than in males. We confirmed that the environmental conditions have an important effect on allometric patterns and body size