Effects of an intensive inpatient rehabilitation program in elderly patients with obesity

Objective: The aim of this study was to assess the short-term effectiveness of an intensive inpatient multidimensional rehabilitation program (MRP), including diet, exercise, and behavioral therapy, in elderly patients with severe obesity. Methods: Forty-four elderly patients (old; age 69.3 \ub1 3.5 years, BMI 41.9 \ub1 14.9) were analyzed against 215 younger patients (young; age 48.2 \ub1 18.5 years, BMI 43.9 \ub1 9.4), who were used as controls. All patients underwent MRP, based on group therapy guided by a multidisciplinary team (physicians, dietitians, exercise trainers, psychologists). We evaluated changes in anthropometry, cardiovascular risk factors, physical fitness, quality of life, and eating behavior. Results: After 3 weeks of MRP, we observed a reduction in body weight (old -3.8%, young -4.3%), BMI (old -3.9%, young -4.4%), waist circumference (old -3.4%, young -4.1%), total cholesterol (old -14.0%, young -15.0%), and fasting glucose (old -8.3%, young -8.1%), as well as improved performance in the Six-Minute-Walk Test (old +28.7%, young +15.3%), chair-stand test (old +24.8%, young +26.9%), and arm-curl test (old +15.2%, young +27.3%). Significant improvement was registered in all other analyzed domains. Conclusion: Our 3-week MRP provided significant clinical and functional improvement, which was similar between elderly and younger patients with severe obesity. In the long-term, this may be translated into better quality of life, through better management of obesity-associated morbidities and reduced frailty

Effects of an Intensive Inpatient Rehabilitation Program in Elderly Patients with Obesity

Objective: The aim of this study was to assess the short-term effectiveness of an intensive inpatient multidimensional rehabilitation program (MRP), including diet, exercise, and behavioral therapy, in elderly patients with severe obesity. Methods: Forty-four elderly patients (old; age 69.3 ± 3.5 years, BMI 41.9 ± 14.9) were analyzed against 215 younger patients (young; age 48.2 ± 18.5 years, BMI 43.9 ± 9.4), who were used as controls. All patients underwent MRP, based on group therapy guided by a multidisciplinary team (physicians, dietitians, exercise trainers, psychologists). We evaluated changes in anthropometry, cardiovascular risk factors, physical fitness, quality of life, and eating behavior. Results: After 3 weeks of MRP, we observed a reduction in body weight (old –3.8%, young –4.3%), BMI (old –3.9%, young –4.4%), waist circumference (old –3.4%, young –4.1%), total cholesterol (old –14.0%, young –15.0%), and fasting glucose (old –8.3%, young –8.1%), as well as improved performance in the Six-Minute-Walk Test (old +28.7%, young +15.3%), chair-stand test (old +24.8%, young +26.9%), and arm-curl test (old +15.2%, young +27.3%). Significant improvement was registered in all other analyzed domains. Conclusion: Our 3-week MRP provided significant clinical and functional improvement, which was similar between elderly and younger patients with severe obesity. In the long-term, this may be translated into better quality of life, through better management of obesity-associated morbidities and reduced frailty

Spatial reorganization of telomeres in long-lived quiescent cells

International audienceBackground : The spatiotemporal behavior of chromatin is an important control mechanism of genomic function. Studies in Saccharomyces cerevisiae have broadly contributed to demonstrate the functional importance of nuclear organization. Although in the wild yeast survival depends on their ability to withstand adverse conditions, most of these studies were conducted on cells undergoing exponential growth. In these conditions, as in most eukaryotic cells, silent chromatin that is mainly found at the 32 telomeres accumulates at the nuclear envelope, forming three to five foci. Results : Here, combining live microscopy, DNA FISH and chromosome conformation capture (HiC) techniques, we report that chromosomes adopt distinct organizations according to the metabolic status of the cell. In particular, following carbon source exhaustion the genome of long-lived quiescent cells undergoes a major spatial re-organization driven by the grouping of telomeres into a unique focus or hypercluster localized in the center of the nucleus. This change in genome conformation is specific to quiescent cells able to sustain long-term viability. We further show that reactive oxygen species produced by mitochondrial activity during respiration commit the cell to form a hypercluster upon starvation. Importantly, deleting the gene encoding telomere associated silencing factor SIR3 abolishes telomere grouping and decreases longevity, a defect that is rescued by expressing a silencing defective SIR3 allele competent for hypercluster formation. Conclusions : Our data show that mitochondrial activity primes cells to group their telomeres into a hypercluster upon starvation, reshaping the genome architecture into a conformation that may contribute to maintain longevity of quiescent cells

Le «pré-urbain» : un territoire entre urbain et rural théâtre de transferts culturels

Related to Fig. 3. Animated 3D reconstruction of the entire contact map of long-lived SP cells (isolated from a SP culture by density gradient). Same annotations as in Additional file 2. (GIF 12057 kb

Additional file 3: Figure S2. of Spatial reorganization of telomeres in long-lived quiescent cells

SIR-mediated telomere clustering drives chromosome conformation in the dense fraction of SP cells. a Mean contacts frequencies between 100-kb centromeres windows in G1 (blue) and G0 quiescent cells (red). Black and green curves: contacts between 100-kb segments randomly sampled in both conditions, to illustrate the absence of coverage biases after normalization. b Chromosome organization of WT and sir3∆ quiescent cells (the cryptic mating type locus HML was deleted to prevent pseudo-diploid effect). ii) Normalized contact matrix obtained for hml∆* (left) and hml∆ sir3∆ (right) cells. Color scale: contact frequencies from rare (white) to frequent (dark blue). Red arrowheads: centromeres contacts; green and yellow arrowheads: telomere–telomere contacts in hml∆ and hml∆ sir3∆ G0 cells, respectively. The 3D representations of the hml∆ and hml∆ sir3∆ matrices are represented next to the contact maps. Each chromosome is represented as a chain of beads (1 bead = 20 kb), with color code reflecting the chromosome arm lengths, from short (blue) to long (red) arms. Yellow beads: subtelomeric regions; black beads: centromeres; purple beads: boundaries of the rDNA cluster. c Contact maps of W303 strain during exponentially growth (EXPO, left) and quiescence (G0, right). Red arrowheads: centromere clustering; green and yellow arrowheads: telomere–telomere contacts of two chromosomes (XIII and XV) in expo and G0 cells, respectively. Because of the low sequencing coverage and quality, the signal is not as strong as for data in Fig. 3 and the bins are larger (1 vector: 80 DpnII RFs). d Quantification of colocalization of 30-kb telomeric regions (red dots) compared with the distribution of the colocalization scores (box plot, two standard deviations) computed for 1000 random sets of 32 windows of 30 kb in the genome (excluding centromeric regions). The colocalization score is normalized by the sequencing depth for each dataset

Additional file 1: Figure S1. of Spatial reorganization of telomeres in long-lived quiescent cells

Characterization of the SP silent chromatin hypercluster. a Western blot against Rap1 on crude extracts from exponential, respiratory, or stationary cultures of a WT strain (yAT1684). H2A antibody was used for the loading control. b Representative fluorescent images of wild-type (WT) strains tagged with Rap1-GFP “yAT 1684”, GFP-Sir2 “yAT405”, Sir3-GFP “yAT779” and GFP-Sir4 “yAT431” strains. Overnight liquid cultures were diluted to 0.2 OD600nm/ml and images were acquired after 5 h (1 OD600nm/ml, fermentation phase) and 7 days (40 OD600nm/ml, stationary phase). c Representative fluorescent image of a Rap1-GFP Sir3-mCherry-tagged strain “yAT194” from stationary phase cultures. We note that Sir3 associates with both telomeres and the rDNA in stationary phase cells. d Representative fluorescent images of Rap1-GFP in stationary cultures of WT “yAT1684” and sir4∆ “yAT2092” strains. e Representative fluorescent images of the nucleolar protein Sik1 tagged with mCherry during fermentation, respiration, and stationary phase (“yAT340”). f Representative fluorescent image of Rap1-GFP Dad2-mRFP (Duo1 And Dam1 interacting, an essential component of the microtubule–kinetochore interface) tagged stationary phase cells (“yAT2279”). g Representative fluorescent image of Sir3-mCherry Cse4-GFP-tagged strain “yAT2280” from stationary phase. Scale bar is 1 μm. (PDF 1343 kb

Additional file 5: Figure S3. of Spatial reorganization of telomeres in long-lived quiescent cells

Telomere hyperclustering is not due to slow growth. a Representative fluorescent image of Rap1-GFP tagged strain grown either at 30 °C or 25 °C in exponential phase (top) and then starved for 16 h in water before imaging (bottom). b Calcofluor staining of LD and HD fractions of a post DS culture after gradient separation. c Heat shock (HS) assay on the LD and HD fractions used in b. (PDF 11591 kb

Guidi et al. 2015

<p>Raw images corresponding to Guidi et al. 2015.</p> <p>For each figure of the manuscript Guidi et al. containing microscopy data we show Z projection (max intensity) of cropped images normalized to be comparable within each experiment. Here we provide for each crop the corresponding Z stack and the Z projection of the whole field image.</p

JAM-A Acts via C/EBP-alpha to Promote Claudin-5 Expression and Enhance Endothelial Barrier Function

Rationale: Intercellular tight junctions are crucial for correct regulation of the endothelial barrier. Their composition and integrity are affected in pathological contexts, such as inflammation and tumor growth. JAM-A (junctional adhesion molecule A) is a transmembrane component of tight junctions with a role in maintenance of endothelial barrier function, although how this is accomplished remains elusive. Objective: We aimed to understand the molecular mechanisms through which JAM-A expression regulates tight junction organization to control endothelial permeability, with potential implications under pathological conditions. Methods and Results: Genetic deletion of JAM-A in mice significantly increased vascular permeability. This was associated with significantly decreased expression of claudin-5 in the vasculature of various tissues, including brain and lung. We observed that C/EBP-α (CCAAT/enhancer-binding protein-α) can act as a transcription factor to trigger the expression of claudin-5 downstream of JAM-A, to thus enhance vascular barrier function. Accordingly, gain-of-function for C/EBP-α increased claudin-5 expression and decreased endothelial permeability, as measured by the passage of fluorescein isothiocyanate (FITC)-dextran through endothelial monolayers. Conversely, C/EBP-α loss-of-function showed the opposite effects of decreased claudin-5 levels and increased endothelial permeability. Mechanistically, JAM-A promoted C/EBP-α expression through suppression of β-catenin transcriptional activity, and also through activation of EPAC (exchange protein directly activated by cAMP). C/EBP-α then directly binds the promoter of claudin-5 to thereby promote its transcription. Finally, JAM-A–C/EBP-α–mediated regulation of claudin-5 was lost in blood vessels from tissue biopsies from patients with glioblastoma and ovarian cancer. Conclusions: We describe here a novel role for the transcription factor C/EBP-α that is positively modulated by JAM-A, a component of tight junctions that acts through EPAC to up-regulate the expression of claudin-5, to thus decrease endothelial permeability. Overall, these data unravel a regulatory molecular pathway through which tight junctions limit vascular permeability. This will help in the identification of further therapeutic targets for diseases associated with endothelial barrier dysfunction