Self care programs and multiple sclerosis: Physical therapeutics treatment - literature review

AbstractObjectiveTo clarify the therapeutic education program impact with multiple sclerosis patients, literature review. Highlight contents and efficacy.MethodA non-systematic review on Medline, PubMed and Cochrane library databases from 1966 to 2010 using the following keywords: “multiple sclerosis”, “self-care”, “self-management” and specific symptoms keywords. Clinical trials and randomized clinical trials, as well as literature reviews published in English, French and German will be analyzed.ResultsCounseling is a part of the non-pharmacological management of chronic illnesses such as multiple sclerosis. Symptoms’ diversity and the different clinical forms limit standardized programs of self-care management, applicable to patients. In the literature review, counseling programs have often low metrology. A behavior change with patients and medical staff could exist. To empower the patient, to reduce symptoms’ impact and to improve treatment access are the aims of educational therapy.ConclusionTherapeutic education program for multiple sclerosis patients could progress with their standardization and assessment, for each sign. To promote the educational therapy of multiple sclerosis patients, a specific training for medical staff, as specific financing are necessary

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

Excursion Ardèche (13-15 mai 1977)

International audienceLes massifs hercyniens ont été longuement érodés pendant le Permien. Des sédiments gréseux et dolomitiques du Trias se sont ensuite déposés sur une plate-forme uniformisée et peu profonde. Toutefois la monotonie de l'ensemble n'excluait pas l'influence de reliefs sous-marins d'origine hercynienne. Les termes liasiques montrent à la fois une épaisseur réduite et des variations de faciès dues à une plate-forme sous-marine instable. Les influences obéissent d'une part à la direction cévenole (NE-SW) et d'autre part à une direction qui lui est orthogonale. A partir du Callovien les conditions deviennent homogènes dans l'ensemble de la région et paraissent le rester jusque dans le Jurassique terminal

Diverse transcription influences can be insulated by the Drosophila SF1 chromatin boundary

Chromatin boundaries regulate gene expression by modulating enhancer–promoter interactions and insulating transcriptional influences from organized chromatin. However, mechanistic distinctions between these two aspects of boundary function are not well understood. Here we show that SF1, a chromatin boundary located in the Drosophila Antennapedia complex (ANT-C), can insulate the transgenic miniwhite reporter from both enhancing and silencing effects of surrounding genome, a phenomenon known as chromosomal position effect or CPE. We found that the CPE-blocking activity associates with different SF1 sub-regions from a previously characterized insulator that blocks enhancers in transgenic embryos, and is independent of GAF-binding sites essential for the embryonic insulator activity. We further provide evidence that the CPE-blocking activity cannot be attributed to an enhancer-blocking activity in the developing eye. Our results suggest that SF1 contains multiple non-overlapping activities that block diverse transcriptional influences from embryonic or adult enhancers, and from positive and negative chromatin structure. Such diverse insulating capabilities are consistent with the proposed roles of SF1 to functionally separate fushi tarazu (ftz), a non-Hox gene, from the enhancers and the organized chromatin of the neighboring Hox genes

An RNA Polymerase III-Dependent Heterochromatin Barrier at Fission Yeast Centromere 1

Heterochromatin formation involves the nucleation and spreading of structural and epigenetic features along the chromatin fiber. Chromatin barriers and associated proteins counteract the spreading of heterochromatin, thereby restricting it to specific regions of the genome. We have performed gene expression studies and chromatin immunoprecipitation on strains in which native centromere sequences have been mutated to study the mechanism by which a tRNAAlanine gene barrier (cen1 tDNAAla) blocks the spread of pericentromeric heterochromatin at the centromere of chromosome 1 (cen1) in the fission yeast, Schizosaccharomyces pombe. Within the centromere, barrier activity is a general property of tDNAs and, unlike previously characterized barriers, requires the association of both transcription factor IIIC and RNA Polymerase III. Although the cen1 tDNAAla gene is actively transcribed, barrier activity is independent of transcriptional orientation. These findings provide experimental evidence for the involvement of a fully assembled RNA polymerase III transcription complex in defining independent structural and functional domains at a eukaryotic centromere

A Single Heterochromatin Boundary Element Imposes Position-Independent Antisilencing Activity in Saccharomyces cerevisiae Minichromosomes

Chromatin boundary elements serve as cis-acting regulatory DNA signals required to protect genes from the effects of the neighboring heterochromatin. In the yeast genome, boundary elements act by establishing barriers for heterochromatin spreading and are sufficient to protect a reporter gene from transcriptional silencing when inserted between the silencer and the reporter gene. Here we dissected functional topography of silencers and boundary elements within circular minichromosomes in Saccharomyces cerevisiae. We found that both HML-E and HML-I silencers can efficiently repress the URA3 reporter on a multi-copy yeast minichromosome and we further showed that two distinct heterochromatin boundary elements STAR and TEF2-UASrpg are able to limit the heterochromatin spreading in circular minichromosomes. In surprising contrast to what had been observed in the yeast genome, we found that in minichromosomes the heterochromatin boundary elements inhibit silencing of the reporter gene even when just one boundary element is positioned at the distal end of the URA3 reporter or upstream of the silencer elements. Thus the STAR and TEF2-UASrpg boundary elements inhibit chromatin silencing through an antisilencing activity independently of their position or orientation in S. cerevisiae minichromosomes rather than by creating a position-specific barrier as seen in the genome. We propose that the circular DNA topology facilitates interactions between the boundary and silencing elements in the minichromosomes

Evaluation of Greenbug and Yellow Sugarcane Aphid Feeding Behavior on Resistant and Susceptible Switchgrass Cultivars

Switchgrass (Panicum virgatum L.) is an emerging biofuel crop that serves as host for aphids. To discern the effects of plant age and possible resistance mechanisms, the feeding behavior of greenbugs (Schizaphis graminum Rondani.) and the yellow sugarcane aphid (Sipha flava Forbes.) was monitored on three diverse switchgrasses by the electrical penetration graph (EPG) technique. Callose deposition and genes associated with callose metabolism were also analyzed to discern their association with plant resistance. There was a strong host effect on greenbugs feeding on lowland cultivar Kanlow at the V3 stage of development, as compared to the greenbug-susceptible upland cultivar Summer and plants derived from Kanlow (♂) × Summer (♀) (K×S) crosses. These data confirmed that Kanlow at the V3 stage had antibiosis to greenbugs, which was absent in the Summer and K×S plants. In contrast, similar effects were not observed for yellow sugarcane aphids, excluding significant differences in the time to first probe on Kanlow plants at the V1 stage and reduction in time spent on pathway processes on Kanlow plants at the V3 stage. These data demonstrated that Kanlow plants may have multiple sources of resistance to the two aphids, and possibly some were phloem based. Microscopy of leaf sections stained with aniline blue for callose was suggestive of increased callose deposition in the sieve elements in Kanlow plants relative to Summer and K×S plants. RT-qPCR analysis of several genes associated with callose metabolism in infested plants was equivocal. Overall, these studies suggest the presence of multiple defense mechanisms against aphids in Kanlow plants, relative to Summer and K×S plants

Predicting hospital stay, mortality and readmission in people admitted for hypoglycaemia: prognostic models derivation and validation

Aims/hypothesis: Hospital admissions for hypoglycaemia represent a significant burden on individuals with diabetes and have a substantial economic impact on healthcare systems. To date, no prognostic models have been developed to predict outcomes following admission for hypoglycaemia. We aimed to develop and validate prediction models to estimate risk of inpatient death, 24 h discharge and one month readmission in people admitted to hospital for hypoglycaemia. Methods: We used the Hospital Episode Statistics database, which includes data on all hospital admission to National Health Service hospital trusts in England, to extract admissions for hypoglycaemia between 2010 and 2014. We developed, internally and temporally validated, and compared two prognostic risk models for each outcome. The first model included age, sex, ethnicity, region, social deprivation and Charlson score (‘base’ model). In the second model, we added to the ‘base’ model the 20 most common medical conditions and applied a stepwise backward selection of variables (‘disease’ model). We used C-index and calibration plots to assess model performance and developed a calculator to estimate probabilities of outcomes according to individual characteristics. Results: In derivation samples, 296 out of 11,136 admissions resulted in inpatient death, 1789/33,825 in one month readmission and 8396/33,803 in 24 h discharge. Corresponding values for validation samples were: 296/10,976, 1207/22,112 and 5363/22,107. The two models had similar discrimination. In derivation samples, C-indices for the base and disease models, respectively, were: 0.77 (95% CI 0.75, 0.80) and 0.78 (0.75, 0.80) for death, 0.57 (0.56, 0.59) and 0.57 (0.56, 0.58) for one month readmission, and 0.68 (0.67, 0.69) and 0.69 (0.68, 0.69) for 24 h discharge. Corresponding values in validation samples were: 0.74 (0.71, 0.76) and 0.74 (0.72, 0.77), 0.55 (0.54, 0.57) and 0.55 (0.53, 0.56), and 0.66 (0.65, 0.67) and 0.67 (0.66, 0.68). In both derivation and validation samples, calibration plots showed good agreement for the three outcomes. We developed a calculator of probabilities for inpatient death and 24 h discharge given the low performance of one month readmission models. Conclusions/interpretation: This simple and pragmatic tool to predict in-hospital death and 24 h discharge has the potential to reduce mortality and improve discharge in people admitted for hypoglycaemia

Nucleoporin Mediated Nuclear Positioning and Silencing of HMR

The organization of chromatin domains in the nucleus is an important factor in gene regulation. In eukaryotic nuclei, transcriptionally silenced chromatin clusters at the nuclear periphery while transcriptionally poised chromatin resides in the nuclear interior. Recent studies suggest that nuclear pore proteins (NUPs) recruit loci to nuclear pores to aid in insulation of genes from silencing and during gene activation. We investigated the role of NUPs at a native yeast insulator and show that while NUPs localize to the native tDNA insulator adjacent to the silenced HMR domain, loss of pore proteins does not compromise insulation. Surprisingly we find that NUPs contribute to silencing at HMR and are able to restore silencing to a silencing-defective HMR allele when tethered to the locus. We show that the perinuclear positioning of heterochromatin is important for the NUP-mediated silencing effect and find that loss of NUPs result in decreased localization of HMR to the nuclear periphery. We also show that loss of telomeric tethering pathways does not eliminate NUP localization to HMR, suggesting that NUPs may mediate an independent pathway for HMR association with the nuclear periphery. We propose that localization of NUPs to the tDNA insulator at HMR helps maintain the intranuclear position of the silent locus, which in turn contributes to the fidelity of silencing at HMR

Involvement of yeast HSP90 isoforms in response to stress and cell death induced by acetic acid

Acetic acid-induced apoptosis in yeast is accompanied by an impairment of the general protein synthesis machinery, yet paradoxically also by the up-regulation of the two isoforms of the heat shock protein 90 (HSP90) chaperone family, Hsc82p and Hsp82p. Herein, we show that impairment of cap-dependent translation initiation induced by acetic acid is caused by the phosphorylation and inactivation of eIF2 alpha by Gcn2p kinase. A microarray analysis of polysome-associated mRNAs engaged in translation in acetic acid challenged cells further revealed that HSP90 mRNAs are over-represented in this polysome fraction suggesting preferential translation of HSP90 upon acetic acid treatment. The relevance of HSP90 isoform translation during programmed cell death (PCD) was unveiled using genetic and pharmacological abrogation of HSP90, which suggests opposing roles for HSP90 isoforms in cell survival and death. Hsc82p appears to promote survival and its deletion leads to necrotic cell death, while Hsp82p is a pro-death molecule involved in acetic acid-induced apoptosis. Therefore, HSP90 isoforms have distinct roles in the control of cell fate during PCD and their selective translation regulates cellular response to acetic acid stress.This work was supported by Fundacao para a Ciencia e Tecnologia and COMPETE/QREN/EU (PTDC/BIA-MIC/114116/2009), and by the Canadian Institute for Health Research (MOP 89737 to MH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript