Exercise improves immune function, antidepressive response, and sleep quality in patients with chronic primary insomnia

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Hindawi Publishing Corporation BioMed Research International Volume 2014, Article ID 498961, 7 pages http://dx.doi.org/10.1155/2014/498961 Clinical Study Exercise Improves Immune Function, Antidepressive Response, and Sleep Quality in Patients with Chronic Primary Insomnia Giselle Soares Passos,1 Dalva Poyares,2 Marcos Gonçalves Santana,1 Alexandre Abílio de Souza Teixeira,2 Fábio Santos Lira,3 Shawn D. Youngstedt,4,5 Ronaldo Vagner Thomatieli dos Santos,2 Sergio Tufik,2 and Marco Túlio de Mello2,6 1 Universidade Federal de Goiás, Jataı́, GO, Brazil Universidade Federal de São Paulo, São Paulo, SP, Brazil 3 Universidade Estadual Paulista “Júlio de Mesquita Filho”, Presidente Prudente, SP, Brazil 4 College of Nursing and Health Innovation, and Exercise and Wellness, Arizona State University, Phoenix, AZ, USA 5 Phoenix VA Health Care System, Phoenix, AZ, USA 6 Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil 2 Correspondence should be addressed to Giselle Soares Passos; passos.gs@gmail.com Received 16 March 2014; Revised 18 August 2014; Accepted 19 August 2014; Published 21 September 2014 Academic Editor: Esteban Martinez Copyright © 2014 Giselle Soares Passos et al. his is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. he aim of this study was to evaluate the efects of moderate aerobic exercise training on sleep, depression, cortisol, and markers of immune function in patients with chronic primary insomnia. Twenty-one sedentary participants (16 women aged 44.7 ± 9 years) with chronic primary insomnia completed a 4-month intervention of moderate aerobic exercise. Compared with baseline, polysomnographic data showed improvements following exercise training. Also observed were reductions in depression symptoms and plasma cortisol. Immunologic assays revealed a signiicant increase in plasma apolipoprotein A (140.9 ± 22 to 151.2 ± 22 mg/dL) and decreases in CD4 (915.6 ± 361 to 789.6 ± 310 mm3 ) and CD8 (532.4 ± 259 to 435.7 ± 204 mm3 ). Decreases in cortisol were signiicantly correlated with increases in total sleep time (� = −0.51) and REM sleep (� = −0.52). In summary, long-term moderate aerobic exercise training improved sleep, reduced depression and cortisol, and promoted signiicant changes in immunologic variables. 1. Introduction Chronic primary insomnia is a prevalent condition that afects 10–15% of the adult population, predominantly women [1]. Insomnia is particularly prevalent later in life, afecting approximately 12–25% of healthy seniors, and the prevalence is even higher among older adults with coexisting medical or psychiatric disorders [2]. Insomnia is oten associated with occupational and psychosocial impairments, such as daytime fatigue, mood disturbances, cognitive deicits, and poor quality of life [3]. Some evidence suggests that sleep disturbances in depressed individuals are associated with impaired immune function [4, 5]; lower NK cell activity [6] and signiicantly lower levels of immune cells (CD3+, CD4+, and CD8+) [7] are associated with chronic insomnia. Although the most common treatment for insomnia is pharmacotherapy, this type of treatment is associated with mortality [8] and other negative risk factors. hus, nonpharmacological interventions have been suggested for the treatment of insomnia. Cognitive and behavioral therapies have been the most common nonpharmacological treatments [9, 10]. However, considering the high cost of maintaining these therapies, new nonpharmacological alternatives have been suggested, including regular exercise [11]. 2 Acute [12] and chronic aerobic exercise [13–15] studies have demonstrated signiicant reductions in insomnia. Among the positive efects of aerobic exercise on health is the promotion of immune function [16]. he objective of the present study was to evaluate the efects of aerobic exercise on sleep, depression symptoms, immune function, and cortisol levels among patients with chronic primary insomnia. 2. Methods he study was approved by the University Human Research Ethics Committee and conformed to the principles outlined in the Declaration of Helsinki. he participants were recruited through advertisements in newspapers, magazines, and radio shows. 2.1. Screening. Interested prospective participants contacted the laboratory and were initially screened in a phone interview. he initial inclusion criteria included being between 30 and 55 years old; having insomnia complaints for longer than 6 months; and having at least one complaint of daytime impairment resulting from insomnia (i.e., mood, cognition, or perception of fatigue). he initial exclusion criteria included the use of medication or psychotherapeutic drugs for insomnia or other psychiatric disorders, shitwork, and exercising ≥1 day per week. Prospective participants who passed the phone screen were invited to the laboratory for further orientation to the study and screening. During the visit, the prospective participants signed a written informed consent form approved by the ethics committee. Further medical screening included establishing a clinical diagnosis of primary insomnia according to the DSM-IV [17] and the American Academy of Sleep Medicine [18] for a period longer than 6 months. Additional exclusion criteria included blood tests contraindicating participation in exercise, having major depression (i.e., a Beck Depression Inventory score >20; [19], having an apnea-hypopnea index (AHI) >15, having a periodic leg movement index (PLMI) >15, and being a shit worker or all-night worker). he participants received a clinical consultation and an electrocardiogram at rest and under maximal stress during cardiopulmonary exercise testing (CPET). he CPET was performed on a treadmill (Life Fitness 9500 HR) with an initial velocity of 4 km/h, increasing the speed by 0.5 km/h each minute until voluntary exhaustion. Breath-by-breath assessments were collected using a metabolic system (Quark ̇ 2 value obtained during PFT4, Rome, Italy). he highest VO the last 20 seconds of the test was considered to be the peak ̇ 2 peak). he ventilatory threshold (VT1 ) oxygen uptake (VO ̇ was estimated by inspecting the inlection point of VCO 2 ̇ 2 (modiied V-slope) [20, 21]. A certiicate with respect to VO attesting to the patient’s ability to participate in the exercise protocol was provided by his or her physician and served as the inal requirement for participation in the study. 2.2. Exercise Training. Following screening, the participants performed the exercise training regimen for 4 months. BioMed Research International Exercise was performed 3 days per week for 50 continuous minutes per bout at the VT1 [20, 21], established during the CPET. he timing of the exercise was randomized to occur in the morning (10:00 ± 1 h) or in the evening (18:00 ± 1 h). 2.3. Polysomnographic Measures. he participants underwent polysomnographic (PSG) recording at the Sleep Institute before and ater the exercise training. For the preintervention assessment, PSG recording was performed over 2 nights. he irst night served as an adaption night; 48 hr later, the participants returned for another night of PSG recording. he posttraining PSG assessment occurred at least 30 hours ater the last exercise session. he participants arrived at the sleep laboratory at 21:00; the PSG recording started and inished according to each volunteer’s habitual sleep schedule. he digital system EMBLA was used (EMBLA S7000, Embla Systems Inc., CO, USA). he measured variables included total sleep time (TST), sleep eiciency (the ratio between total sleep time and total recorded time multiplied by 100), sleep onset latency, waking ater sleep onset, arousals, sleep stages (I, II, III, and IV of NREM sleep and REM sleep), and the latencies for each sleep stage, including Stage 1, Stage 2, Stages 3 and 4, and REM. he apnea-hypopnea index (AHI) and periodic leg movements (PLM) were also measured. Two researchers who were blinded to the study design performed the staging and analyzed the PSG events using international criteria [22–24]. 2.4. Questionnaires and Blood Draw. Approximately twentyfour hours ater the PSG assessment, the subjects arrived in the laboratory at 9 a.m. hey completed the Pittsburgh Sleep Quality Index [25] and Beck Depression Inventory [19]. At approximately 10-11 a.m. preprandial venous blood was drawn from the medial cubital vein. 2.5. Immunologic Assays 2.5.1. Immunological Measures. Total leukocyte and subgroup cell counts were determined using an automated hematology analyzer (Advia 120, Siemens). CD4 and CD8 populations were determined by low cytometry using the CD3/CD4 or CD3/CD8 expression in the cell surface (FACSCalibur, Becton Dickison, San Jose, CA, USA). 2.5.2. Cortisol and Apolipoprotein. Plasma cortisol concentrations were determined using a chemiluminescence immunoassay (Unicell DXI, Beckman Coulter, Fullerton, CA, USA), CV% within assay: 4.4. CRP was determined by nephelometry (Image 800, Beckman Coulter), CV% within assay: 5.0. Apolipoprotein A (ApoA) and apolipoprotein B (ApoB) were measured using nephelometry (Image 800, Beckman Colter), CV% within assay: 4.0. 2.6. Statistical Analysis. he program STATISTICA (Statsot, Inc., version 7.0) was used for data analysis. We tested normality by Shapiro Wilk’s test. For normally distributed data we used Student’s paired �-test (to compare the pre- and postexercise measures) and for data that violated normality BioMed Research International 3 267 patients assessed for eligibility 229 excluded 47 were excluded for having reported a previous diagnosis of depression 20 for having reported a diagnosis of other psychiatric disorders 39 for practicing systematic physical exercise 16 for working in shifts 15 for an apnea-hypopnea index or a periodic leg movement index >15 70 for having reported the regular use of medication for insomnia 22 for not presenting evidence of insomnia at the time of evaluation. Screening: 38 participants 17 participants drop out Baseline: 21 participants After exercise: 21 participants Figure 1: Participant lowchart. Table 1: Physiological parameters. Variable BMI (kg/m2 ) VO2peak (mL/kg/min) Speed VT1 (km/h) Baseline (� = 21) 24.7 ± 5 28.4 ± 7 5.3 ± 1 Ater exercise (� = 21) 24.6 ± 5 30.3 ± 6 6.1 ± 1 � ns ns <.001 Wilcoxon matched pairs test, signiicant results, � < .05; data are expressed as mean ± SD. VO2peak : peak oxygen consumption; VT1 : irst ventilatory threshold. we used Wilcoxon matched pairs test. Spearman’s correlation coeicient was performed to assess associations between immune system variables and sleep data (ater exercisebaseline means). he data are expressed as the mean ± SD. he level of statistical signiicance was set at � < .05. 3. Results 3.1. Recruitment, Participant Attrition, and Adherence to the Exercise Protocol. Two hundred sixty-seven people contacted the researchers by telephone or email with interest in participating in the study. Of this total, 229 were excluded because they did not meet the inclusion criteria (Figure 1). hirtyeight participants (29 women) passed the initial screening. However, before beginning the exercise training protocol, 3 men and 5 women withdrew from the study during the preintervention period. hus, the exercise protocol began with a sample of 30 participants. However during the irst month of the study 11 participants drop out. Of these, 9 (30%) dropped out because of problems with the program schedule, which could not be changed during the study. As a result, the inal sample size was 21. hese 21 participants exhibited good adherence to the study protocol (>90%) based on their class attendance and the percentage of the exercise time they spent within the prescribed intensity (90%). 3.2. Physiological Parameters. Signiicant increase in speed in VT1 (5.3±1 to 6.1±1 km/h, � < .001) was found ater exercise training (Table 1). 4 BioMed Research International Table 2: Polysomnography variables on the baseline and ater exercise. Variable TST (hours) ∗ SOL (min) LREM (min) SE (%) ∗ WASO (min) Arousals (events/hour) Stage 1 (%) ∗ Stage 2 (%) Stage 3 (%) Stage 4 (%) REM sleep (%) ∗ Latency of Stage 1 (min) ∗ Latency of Stage 2 (min) ∗ Latency of Stages 3 and 4 (min) ∗ AHI (events/hour) ∗ PLM (events/hour) Baseline (� = 21) 5.7 ± 0.8 22.5 ± 23 100.4 ± 38 82.2 ± 10 53.2 ± 49 17.8 ± 23 3.9 ± 2 56.7 ± 7 4.6 ± 2 15.3 ± 5 19.4 ± 6 80.6 ± 89 23.6 ± 23 55.6 ± 51 9.7 ± 9 2.0 ± 4 Ater exercise (� = 21) 6.1 ± 0.5 8.6 ± 8 76.0 ± 43 88.9 ± 8 38.2 ± 25 15.6 ± 13 3.9 ± 3 54.5 ± 8 5.1 ± 2 14.5 ± 6 21.9 ± 6 38. 9 ± 77 10.5 ± 11 33.7 ± 18 8.1 ± 9 2.2 ± 5 � .02 <.001 .01 .006 .03 ns ns ns ns ns .04 ns .01 .04 ns ns Paired Student’s �-test or ∗ Wilcoxon matched pairs test, signiicant results, � < .05; data are expressed as mean ± SD. TST: total sleep time; SE: sleep eiciency; SOL: sleep onset latency; REM: rapid eye movements; LREM: REM sleep latency; TWT: total wake time; WASO: wake time ater sleep onset; AHI: apnea hypopnea index; PLM: periodic leg movements. 3.3. Polysomnography. Compared with baseline, signiicant reductions were observed in sleep onset latency (approximately 14 min, � < .01), wake ater sleep onset (approximately 15 min, � = .03), and REM latency (approximately 24 min �(29) = 0.01), and signiicant increases were found in total sleep time (approximately 24 min, �(29) = 0.02) and sleep eiciency (approximately 7%, �(29) = 0.002) in the postexercise evaluation. he percentage of REM sleep increased signiicantly (2.5%, �(29) = 0.04), and the latency of Stage 2 (approximately 13 min, � = .01) and latency of Stages 3 and 4 decreased signiicantly (approximately 22 min, � = .02) (Table 2). in the CD4 (938.8 ± 381 to 778.9 ± 324 mm3 , � < .001) and CD8 counts (572.2 ± 265 to 434.1 ± 197 mm3 , � < .0010) (Table 4). 3.4. Subjective Scales. Subjective sleep rating on the Pittsburgh Sleep Quality Index (PSQI) revealed signiicant improvement on the subjective sleep duration (approximately 1 h, �(29) < 0.001) and a signiicant reduction in sleep onset latency (24 min, � = .005) following exercise training compared with preintervention. he global score on the PSQI was reduced signiicantly (approximately 40%, �(29) < .0001) ater the exercise intervention. he Beck Depression Inventory score decreased signiicantly ater exercise training (approximately 30%, �(29) = 0.04) (Table 3). 4. Discussion 3.5. Immune Proile. We observed a reduction in plasma cortisol concentrations ater exercise training (13.7 ± 5 to 10.6 ± 4 �g/dL, � = .02). Plasma apolipoprotein A increased (139.2 ± 26 to 153.9 ± 24 mg/dL, � < .001), and erythrocytes (4.8 ± 0.4 to 4.6 ± 0.4 106 /mm3 , � = .02), total leukocytes (6.8±1 to 5.7±2 mil/mm3 , � < .001), monocytes (0.39±0.2 to 0.26±0.1 mil/mm3 , � < .001), and typical lymphocytes (2.1± 0.7 to 1.7 ± 0.5 mil/mm3 , � < .001) decreased signiicantly ater the intervention. We also observed signiicant decreases 3.6. Correlation of Immunity and Cortisol with Sleep Data. Signiicant correlations between the decrease in cortisol and increases in polysomnographic measures of total sleep time (� = −0.50, � < .05) and REM sleep (� = −0.47, � < .05) were observed. here were no signiicant correlations between changes in cortisol or immunity measures and changes in subjective or objective sleep data. he purpose of this study was to investigate the efects of exercise training on sleep, depression symptoms, immunity, and cortisol levels of patients with chronic primary insomnia. he results showed signiicant improvements in objective and subjective sleep and a reduction in depression symptoms ater exercise training. Moreover, there were decreases in plasma cortisol levels and changes in the immunologic parameters, which were correlated with some of the sleep improvements. he results are consistent with previous research showing the beneits of exercise training on sleep and depression symptoms among patients with chronic primary insomnia [12, 14, 15]. It has been suggested that persistent hyperarousal at autonomous, emotional, cognitive, or neurobiological levels may be the decisive factor in the development and persistence of chronic primary insomnia [26–28]. his pathway could be attenuated by well-established anxiety-reducing efects of exercise [29]. BioMed Research International 5 Table 3: Subjective scales on baseline and postexercise evaluations. Baseline (� = 21) 11.2 ± 3 46.5 ± 22 75.3 ± 29 4.6 ± 2 9.3 ± 3 Variable PSQI (score) ∗ PSQI-SOL (min) PSQI-SE (%) PSQI-TST (h) BDI (score) Ater exercise (� = 21) 6.8 ± 2 22.0 ± 10# 81.8 ± 17 6.3 ± 2 6.5 ± 5 � .001 .005 Ns .001 .04 Paired Student’s �-test or ∗ Wilcoxon matched pairs test, signiicant results, � < .05; # � = 20; data are expressed as mean ± SD. PSQI: Pittsburgh Sleep Quality Index; BDI: Beck Depression Inventory. Table 4: Cortisol and immune proile of volunteers on the baseline and ater exercise. Variable Cortisol (�g/dL) CD4 (mm3 ) CD8 (mm3 ) CD4 : CD8 C-reactive protein (mg/dL) Apolipoprotein A (mg/dL) Apolipoprotein B (mg/dL) Immunoglobulin A (mg/dL) Hematocrit (%) Erythrocytes (106 /mm3 ) Hemoglobin (g/dL) Total leukocytes (mil/mm3 ) Neutrophils (mil/mm3 ) Monocytes (mil/mm3 ) Typical lymphocytes (mil/mm3 ) Eosinophils (mil/mm3 ) Basophils (mil/mm3 ) Platelets (mil/mm3 ) Baseline (� = 21) 13.7 ± 5 938.8 ± 381 572.2 ± 265 1.77 ± 0.6 0.22 ± 0.2 139.2 ± 26 98.1 ± 26 259.6 ± 123 42.0 ± 4 4.8 ± 0.4 14.0 ± 1 6.8 ± 1 4.1 ± 1 0.39 ± 0.2 2.1 ± 0.7 0.16 ± 0.1 0.05 ± 0.02 271.6 ± 66 Ater exercise (� = 21) 10.6 ± 4 778.9 ± 324 434.1 ± 197 1.9 ± 0.7 0.19 ± 0.1 153.9 ± 24 94.4 ± 21 262.6 ± 103 41.7 ± 4 4.6 ± 0.4 13.7 ± 1 5.7 ± 2 3.6 ± 1 0.26 ± 0.1 1.7 ± 0.5 0.14 ± 0.1 0.04 ± 0.02 276 ± 63 � .02 <.001 <.001 ns ns <.001 ns ns ns .02 ns <.001 ns <.001 <.001 ns ns ns Wilcoxon matched pairs test, signiicant equilibrium value of MeCpG steps (,+14 deg.) [31,44]. In comparison, methylation has a significantly lower stability cost when happening at major groove positions, such as 211 and 21 base pair from dyad (mutations 9 and 12), where the roll of the nucleosome bound conformation (+10 deg.) is more compatible with the equilibrium geometry of MeCpG steps. The nucleosome destabilizing effect of cytosine methylation increases with the number of methylated cytosines, following the same position dependence as the single methylations. The multiple-methylation case reveals that each major groove meth- PLOS Computational Biology | www.ploscompbiol.org 3 November 2013 | Volume 9 | Issue 11 | e1003354 DNA Methylation and Nucleosome Positioning ylation destabilizes the nucleosome by around 1 kJ/mol (close to the average estimate of 2 kJ/mol obtained for from individual methylation studies), while each minor groove methylation destabilizes it by up to 5 kJ/mol (average free energy as single mutation is around 6 kJ/mol). This energetic position-dependence is the reverse of what was observed in a recent FRET/SAXS study [30]. The differences can be attributed to the use of different ionic conditions and different sequences: a modified Widom-601 sequence of 157 bp, which already contains multiple CpG steps in mixed orientations, and which could assume different positioning due to the introduction of new CpG steps and by effect of the methylation. The analysis of our trajectories reveals a larger root mean square deviation (RMSD) and fluctuation (RMSF; see Figures S2– S3 in Text S1) for the methylated nucleosomes, but failed to detect any systematic change in DNA geometry or in intermolecular DNA-histone energy related to methylation (Fig. S1B, S1C, S4–S6 in Text S1). The hydrophobic effect should favor orientation of the methyl group out from the solvent but this effect alone is not likely to justify the positional dependent stability changes in Figure 2, as the differential solvation of the methyl groups in the bound and unbound states is only in the order of a fraction of a water molecule (Figure S5 in Text S1). We find however, a reasonable correlation between methylation-induced changes in hydrogen bond and stacking interactions of the bases and the change in nucleosome stability (see Figure S6 in Text S1). This finding suggests that methylation-induced nucleosome destabilization is related to the poorer ability of methylated DNA to fit into the required conformation for DNA in a nucleosome. Changes in the elastic deformation energy between methylated and un-methylated DNA correlate with nucleosomal differential binding free energies To further analyze the idea that methylation-induced nucleosome destabilization is connected to a worse fit of methylated DNA into the required nucleosome-bound conformation, we computed the elastic energy of the nucleosomal DNA using a harmonic deformation method [36,37,44]. This method provides a rough estimate of the energy required to deform a DNA fiber to adopt the super helical conformation in the nucleosome (full details in Suppl. Information Text S1). As shown in Figure 2, there is an evident correlation between the increase that methylation produces in the elastic deformation energy (DDE def.) and the free energy variation (DDG bind.) computed from MD/TI calculations. Clearly, methylation increases the stiffness of the CpG step [31], raising the energy cost required to wrap DNA around the histone octamers. This extra energy cost will be smaller in regions of high positive roll (naked DNA MeCpG steps have a higher roll than CpG steps [31]) than in regions of high negative roll. Thus, simple elastic considerations explain why methylation is better tolerated when the DNA faces the histones through the major groove (where positive roll is required) that when it faces histones through the minor groove (where negative roll is required). Nucleosome methylation can give rise to nucleosome repositioning We have established that methylation affects the wrapping of DNA in nucleosomes, but how does this translate into chromatin structure? As noted above, accumulation of minor groove methylations strongly destabilizes the nucleosome, and could trigger nucleosome unfolding, or notable changes in positioning or phasing of DNA around the histone core. While accumulation of methylations might be well tolerated if placed in favorable positions, accumulation in unfavorable positions would destabilize the nucleosome, which might trigger changes in chromatin structure. Chromatin could in fact react in two different ways in response to significant levels of methylation in unfavorable positions: i) the DNA could either detach from the histone core, leading to nucleosome eviction or nucleosome repositioning, or ii) the DNA could rotate around the histone core, changing its phase to place MeCpG steps in favorable positions. Both effects are anticipated to alter DNA accessibility and impact gene expression regulation. The sub-microsecond time scale of our MD trajectories of methylated DNAs bound to nucleosomes is not large enough to capture these effects, but clear trends are visible in cases of multiple mutations occurring in unfavorable positions, where unmethylated and methylated DNA sequences are out of phase by around 28 degrees (Figure S7 in Text S1). Due to this repositioning, large or small, DNA could move and the nucleosome structure could assume a more compact and distorted conformation, as detected by Lee and Lee [29], or a slightly open conformation as found in Jimenez-Useche et al. [30]. Using the harmonic deformation method, we additionally predicted the change in stability induced by cytosine methylation for millions of different nucleosomal DNA sequences. Consistently with our calculations, we used two extreme scenarios to prepare our DNA sequences (see Fig. 3): i) all positions where the minor grooves contact the histone core are occupied by CpG steps, and ii) all positions where the major grooves contact the histone core are occupied by CpG steps. We then computed the elastic energy required to wrap the DNA around the histone proteins in unmethylated and methylated states, and, as expected, observed that methylation disfavors DNA wrapping (Figure 3A). We have rescaled the elastic energy differences with a factor of 0.23 to match the DDG prediction in figure 2B. In agreement with the rest of our results, our analysis confirms that the effect of methylation is position-dependent. In fact, the overall difference between the two extreme methylation scenarios (all-in-minor vs all-in-major) is larger than 60 kJ/mol, the average difference being around 15 kJ/ mol. We have also computed the elastic energy differences for a million sequences with CpG/MeCpG steps positioned at all possible intermediate locations with respect to the position (figure 3B). The large differences between the extreme cases can induce rotations of DNA around the histone core, shifting its phase to allow the placement of the methylated CpG steps facing the histones through the major groove. It is illustrative to compare the magnitude of CpG methylation penalty with sequence dependent differences. Since there are roughly 1.5e88 possible 147 base pairs long sequence combinations (i.e., (4n+4(n/2))/2, n = 147), it is unfeasible to calculate all the possible sequence effects. However, using our elastic model we can provide a range of values based on a reasonably large number of samples. If we consider all possible nucleosomal sequences in the yeast genome (around 12 Mbp), the energy difference between the best and the worst sequence that could form a nucleosome is 0.7 kj/mol per base (a minimum of 1 kJ/mol and maximum of around 1.7 kJ/mol per base, the first best and the last worst sequences are displayed in Table S3 in Text S1). We repeated the same calculation for one million random sequences and we obtained equivalent results. Placing one CpG step every helical turn gives an average energetic difference between minor groove and major groove methylation of 15 kJ/ mol, which translates into ,0.5 kJ/mol per methyl group, 2 kJ/ mol per base for the largest effects. Considering that not all nucleosome base pair steps are likely to be CpG steps, we can conclude that the balance between the destabilization due to CpG methylation and sequence repositioning will depend on the PLOS Computational Biology | www.ploscompbiol.org 4 November 2013 | Volume 9 | Issue 11 | e1003354 DNA Methylation and Nucleosome Positioning Figure 3. Methylated and non-methylated DNA elastic deformation energies. (A) Distribution of deformation energies for 147 bplong random DNA sequences with CpG steps positioned every 10 base steps (one helical turn) in minor (red and dark red) and major (light and dark blue) grooves respectively. The energy values were rescaled by the slope of a best-fit straight line of figure 2, which is 0.23, to por la lectura a través de la lectura de la prensa. La educación en los medios las fuerzas dispersas en función de los soportes mediáticos y orientarse más hacia la educación en medios que al dominio adquiere pleno derecho y entidad en la sección sexta titulada «competencias sociales y cívi- técnico de los aparatos. cas» que indica que «los alum- nos deberán ser capaces de juz- gar y tendrán espíritu crítico, lo que supone ser educados en los las programaciones oficiales, ya que, a lo largo de un medios y tener conciencia de su lugar y de su influencia estudio de los textos, los documentalistas del CLEMI en la sociedad». han podido señalar más de una centena de referencias a la educación de los medios en el seno de disciplinas 4. Un entorno positivo como el francés, la historia, la geografía, las lenguas, Si nos atenemos a las cifras, el panorama de la las artes plásticas : trabajos sobre las portadas de educación en medios es muy positivo. Una gran ope- prensa, reflexiones sobre temas mediáticos, análisis de ración de visibilidad como la «Semana de la prensa y publicidad, análisis de imágenes desde todos los ángu- de los medios en la escuela», coordinada por el CLE- los, reflexión sobre las noticias en los países europeos, MI, confirma año tras año, después de 17 convocato- información y opinión rias, el atractivo que ejerce sobre los profesores y los Esta presencia se constata desde la escuela mater- alumnos. Concebida como una gran operación de nal (2 a 6 años) donde, por ejemplo, se le pregunta a complementariedad entre la escuela y los profesiona- los niños más pequeños si saben diferenciar entre un les de los medios, alrededor del aprendizaje ciudada- periódico, un libro, un catálogo, a través de activida- no de la comunicación mediática, este evento moviliza des sensoriales, si saben para qué sirve un cartel, un durante toda una semana un porcentaje elevado de periódico, un cuaderno, un ordenador si son capa- centros escolares que representan un potencial de 4,3 ces de reconocer y distinguir imágenes de origen y de millones de alumnos (cifras de 2006). Basada en el naturaleza distintas. Podríamos continuar con más voluntariado, la semana permite desarrollar activida- ejemplos en todos los niveles de enseñanza y práctica- des más o menos ambiciosas centradas en la introduc- Páginas 43-48 ción de los medios en la vida de la escuela a través de la instalación de kioscos, organización de debates con profesionales y la confección por parte de los alumnos de documentos difundidos en los medios profesionales. Es la ocasión de dar un empujón a la educación en medios y de disfrutarlos. Los medios –un millar en 2006– se asocian de maneras diversas ofreciendo ejemplares de periódicos, acceso a noticias o a imágenes, proponiendo encuentros, permitiendo intervenir a los jóvenes en sus ondas o en sus columnas Esta operación da luz al trabajo de la educación en medios y moviliza a los diferentes participantes en el proyecto. 5. La formación de los docentes La formación es uno de los pilares principales de la educación en los medios. Su función es indispensable ya que no se trata de una disciplina, sino de una enseñanza que se hace sobre la base del voluntariado y del compromiso personal. Se trata de convencer, de mostrar, de interactuar. En primer lugar es necesario incluirla en la formación continua de los docentes, cuyo volumen se ha incrementado desde 1981 con la aparición de una verdadera política de formación continua de personal. Es difícil dar una imagen completa del volumen y del público, pero si nos atenemos a las cifras del CLEMI, hay más de 24.000 profesores que han asistido y se han involucrado durante 2004-05. 5.1. La formación continua En la mayoría de los casos, los profesores reciben su formación en contextos cercanos a su centro de trabajo, o incluso en este mismo. Después de una política centrada en la oferta que hacían los formadores, se valora más positivamente la demanda por parte del profesorado, ya que sólo así será verdaderamente fructífera. Los cursos de formación se repartieron en varias categorías: desde los formatos más tradicionales (cursos, debates, animaciones), hasta actividades de asesoramiento y de acompañamiento, y por supuesto los coloquios que permiten un trabajo en profundidad ya que van acompañados de expertos investigadores y profesionales. Citemos, por ejemplo en 2005, los coloquios del CLEMI-Toulouse sobre el cine documental o el del CLEMI-Dijon sobre «Políticos y medios: ¿connivencia?». Estos coloquios, que forman parte de un trabajo pedagógico regular, reagrupan a los diferentes participantes regionales y nacionales alrededor de grandes temas de la educación en medios y permiten generar nuevos conocimientos de aproximación y una profundización. Páginas 43-48 Hay otro tipo de formación original que se viene desarrollando desde hace menos tiempo, a través de cursos profesionales, como por ejemplo, en el Festival Internacional de Foto-periodismo «Visa para la imagen», en Perpignan. La formación se consolida en el curso, da acceso a las exposiciones, a las conferencias de profesionales y a los grandes debates, pero añade además propuestas pedagógicas y reflexiones didácticas destinadas a los docentes. Estas nuevas modalidades de formación son también consecuencia del agotamiento de la formación tradicional en las regiones. Los contenidos más frecuentes en formación continua conciernen tanto a los temas más clásicos como a los cambios que se están llevando a cabo en las prácticas mediáticas. Así encontramos distintas tendencias para 2004-05: La imagen desde el ángulo de la producción de imágenes animadas, el análisis de la imagen de la información o las imágenes del J.T. La prensa escrita y el periódico escolar. Internet y la información en línea. Medios y educación de los medios. 5.2 La formación inicial La formación inicial está aun en un grado muy ini- cial. El hecho de que la educación en medios no sea una disciplina impide su presencia en los IUFM (Institutos Universitarios de Formación de Maestros) que dan una prioridad absoluta a la didáctica de las disciplinas. En 2003, alrededor de 1.400 cursillistas sobre un total de 30.000 participaron en un momento u otro de un módulo de educación en medios. Estos módulos se ofrecen en función del interés que ese formador encuentra puntualmente y forman parte a menudo de varias disciplinas: documentación, letras, historia-geografía Estamos aún lejos de una política concertada en este dominio. La optativa «Cine-audiovisual» ha entrado desde hace muy poco tiempo en algunos IUFM destinada a obtener un certificado de enseñanza de la opción audiovisual y cine. Internet tiene cabida también en los cursos de formación inicial, recientemente con la aparición de un certificado informático y de Internet para los docentes, dirigido más a constatar competencias personales que a valorar una aptitud para enseñarlos. 6. ¿Y el futuro? El problema del futuro se plantea una vez más por la irrupción de nuevas técnicas y nuevos soportes. La difusión acelerada de lo digital replantea hoy muchas cuestiones relativas a prácticas mediáticas. Muchos Comunicar, 28, 2007 47 Comunicar, 28, 2007 Enrique Martínez-Salanova '2007 para Comunicar 48 trabajos que llevan el rótulo de la educación en medios solicitan una revisión ya que los conceptos cambian. La metodología elaborada en el marco de la educación en medios parece incluso permitir la inclinación de la sociedad de la información hacia una sociedad del conocimiento, como defiende la UNESCO. En Francia, se necesitaría unir las fuerzas dispersas en función de los soportes mediáticos y orientarse más hacia la educación en medios que al dominio técnico de los aparatos. Los avances recientes en el reconocimiento de estos contenidos y las competencias que supondrían podrían permitirlo. Referencias CLEMI/ACADEMIE DE BORDEAUX (Ed.) (2003): Parcours médias au collège: approches disciplinaires et transdisciplinaires. Aquitaine, Sceren-CRDP. GONNET, J. (2001): Education aux médias. Les controverses fécondes. Paris, Hachette Education/CNDP. SAVINO, J.; MARMIESSE, C. et BENSA, F. (2005): L’éducation aux médias de la maternelle au lycée. Direction de l’Enseignement Scolaire. Paris, Ministère de l’Education Nationale, Sceren/CNDP, Témoigner. BEVORT, E. et FREMONT, P. (2001): Médias, violence et education. Paris, CNDP, Actes et rapports pour l’éducation. – www.clemi.org: fiches pédagogiques, rapports et liens avec les pages régionales/académiques. – www.ac-nancy-metz.fr/cinemav/quai.html: Le site «Quai des images» est dédié à l’enseignement du cinéma et de l’audiovisuel. – www.france5.fr/education: la rubrique «Côté profs» a une entrée «education aux médias». – www.educaunet.org: Programme européen d’éducation aux risques liés à Internet. dResedfeleexliobnuetsacón Páginas 43-48
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