Obesity Impact on the Attentional Cost for Controlling Posture

International audienceBACKGROUND: This study investigated the effects of obesity on attentional resources allocated to postural control in seating and unipedal standing. METHODS: Ten non obese adults (BMI = 22.4±1.3, age = 42.4±15.1) and 10 obese adult patients (BMI = 35.2±2.8, age = 46.2±19.6) maintained postural stability on a force platform in two postural tasks (seated and unipedal). The two postural tasks were performed (1) alone and (2) in a dual-task paradigm in combination with an auditory reaction time task (RT). Performing the RT task together with the postural one was supposed to require some attentional resources that allowed estimating the attentional cost of postural control. 4 trials were performed in each condition for a total of 16 trials. FINDINGS: (1) Whereas seated non obese and obese patients exhibited similar centre of foot pressure oscillations (CoP), in the unipedal stance only obese patients strongly increased their CoP sway in comparison to controls. (2) Whatever the postural task, the additional RT task did not affect postural stability. (3) Seated, RT did not differ between the two groups. (4) RT strongly increased between the two postural conditions in the obese patients only, suggesting that body schema and the use of internal models was altered with obesity. INTERPRETATION: Obese patients needed more attentional resources to control postural stability during unipedal stance than non obese participants. This was not the case in a more simple posture such as seating. To reduce the risk of fall as indicated by the critical values of CoP displacement, obese patients must dedicate a strong large part of their attentional resources to postural control, to the detriment of non-postural events. Obese patients were not able to easily perform multitasking as healthy adults do, reflecting weakened psycho-motor abilities

Vestibular signal processing in a subject with somatosensory deafferentation: The case of sitting posture

<p>Abstract</p> <p>Background</p> <p>The vestibular system of the inner ear provides information about head translation/rotation in space and about the orientation of the head with respect to the gravitoinertial vector. It also largely contributes to the control of posture through vestibulospinal pathways. Testing an individual severely deprived of somatosensory information below the nose, we investigated if equilibrium can be maintained while seated on the sole basis of this information.</p> <p>Results</p> <p>Although she was unstable, the deafferented subject (DS) was able to remain seated with the eyes closed in the absence of feet, arm and back supports. However, with the head unconsciously rotated towards the left or right shoulder, the DS's instability markedly increased. Small electrical stimulations of the vestibular apparatus produced large body tilts in the DS contrary to control subjects who did not show clear postural responses to the stimulations.</p> <p>Conclusion</p> <p>The results of the present experiment show that in the lack of vision and somatosensory information, vestibular signal processing allows the maintenance of an active sitting posture (i.e. without back or side rests). When head orientation changes with respect to the trunk, in the absence of vision, the lack of cervical information prevents the transformation of the head-centered vestibular information into a trunk-centered frame of reference of body motion. For the normal subjects, this latter frame of reference enables proper postural adjustments through vestibular signal processing, irrespectively of the orientation of the head with respect to the trunk.</p

5C analysis of the Epidermal Differentiation Complex locus reveals distinct chromatin interaction networks between gene-rich and gene-poor TADs in skin epithelial cells

YesMammalian genomes contain several dozens of large (>0.5 Mbp) lineage-specific gene loci harbouring functionally related genes. However, spatial chromatin folding, organization of the enhancer-promoter networks and their relevance to Topologically Associating Domains (TADs) in these loci remain poorly understood. TADs are principle units of the genome folding and represents the DNA regions within which DNA interacts more frequently and less frequently across the TAD boundary. Here, we used Chromatin Conformation Capture Carbon Copy (5C) technology to characterize spatial chromatin interaction network in the 3.1 Mb Epidermal Differentiation Complex (EDC) locus harbouring 61 functionally related genes that show lineage-specific activation during terminal keratinocyte differentiation in the epidermis. 5C data validated by 3D-FISH demonstrate that the EDC locus is organized into several TADs showing distinct lineage-specific chromatin interaction networks based on their transcription activity and the gene-rich or gene-poor status. Correlation of the 5C results with genome-wide studies for enhancer-specific histone modifications (H3K4me1 and H3K27ac) revealed that the majority of spatial chromatin interactions that involves the gene-rich TADs at the EDC locus in keratinocytes include both intra- and inter-TAD interaction networks, connecting gene promoters and enhancers. Compared to thymocytes in which the EDC locus is mostly transcriptionally inactive, these interactions were found to be keratinocyte-specific. In keratinocytes, the promoter-enhancer anchoring regions in the gene-rich transcriptionally active TADs are enriched for the binding of chromatin architectural proteins CTCF, Rad21 and chromatin remodeler Brg1. In contrast to gene-rich TADs, gene-poor TADs show preferential spatial contacts with each other, do not contain active enhancers and show decreased binding of CTCF, Rad21 and Brg1 in keratinocytes. Thus, spatial interactions between gene promoters and enhancers at the multi-TAD EDC locus in skin epithelial cells are cell type-specific and involve extensive contacts within TADs as well as between different gene-rich TADs, forming the framework for lineage-specific transcription.This study was supported by the grants 5R01AR064580 and 1RO1AR071727 to VAB, TKS and AAS, as well as by the grants from MRC (MR/ M010015/1) and BBSRC (BB/K010050/1) to VAB

Cohesin Protects Genes against γH2AX Induced by DNA Double-Strand Breaks

Chromatin undergoes major remodeling around DNA double-strand breaks (DSB) to promote repair and DNA damage response (DDR) activation. We recently reported a high-resolution map of γH2AX around multiple breaks on the human genome, using a new cell-based DSB inducible system. In an attempt to further characterize the chromatin landscape induced around DSBs, we now report the profile of SMC3, a subunit of the cohesin complex, previously characterized as required for repair by homologous recombination. We found that recruitment of cohesin is moderate and restricted to the immediate vicinity of DSBs in human cells. In addition, we show that cohesin controls γH2AX distribution within domains. Indeed, as we reported previously for transcription, cohesin binding antagonizes γH2AX spreading. Remarkably, depletion of cohesin leads to an increase of γH2AX at cohesin-bound genes, associated with a decrease in their expression level after DSB induction. We propose that, in agreement with their function in chromosome architecture, cohesin could also help to isolate active genes from some chromatin remodelling and modifications such as the ones that occur when a DSB is detected on the genome

The influence of visual flow and perceptual load on locomotion speed

Visual flow is used to perceive and regulate movement speed during locomotion. We assessed the extent to which variation in flow from the ground plane, arising from static visual textures, influences locomotion speed under conditions of concurrent perceptual load. In two experiments, participants walked over a 12-m projected walkway that consisted of stripes that were oriented orthogonal to the walking direction. In the critical conditions, the frequency of the stripes increased or decreased. We observed small, but consistent effects on walking speed, so that participants were walking slower when the frequency increased compared to when the frequency decreased. This basic effect suggests that participants interpreted the change in visual flow in these conditions as at least partly due to a change in their own movement speed, and counteracted such a change by speeding up or slowing down. Critically, these effects were magnified under conditions of low perceptual load and a locus of attention near the ground plane. Our findings suggest that the contribution of vision in the control of ongoing locomotion is relatively fluid and dependent on ongoing perceptual (and perhaps more generally cognitive) task demands

Unravelling higher order chromatin organisation through statistical analysis

Recent technological advances underpinned by high throughput sequencing have given new insights into the three-dimensional structure of mammalian genomes. Chromatin conformation assays have been the critical development in this area, particularly the Hi-C method which ascertains genome-wide patterns of intra and inter-chromosomal contacts. However many open questions remain concerning the functional relevance of such higher order structure, the extent to which it varies, and how it relates to other features of the genomic and epigenomic landscape. Current knowledge of nuclear architecture describes a hierarchical organisation ranging from small loops between individual loci, to megabase-sized self-interacting topological domains (TADs), encompassed within large multimegabase chromosome compartments. In parallel with the discovery of these strata, the ENCODE project has generated vast amounts of data through ChIP-seq, RNA-seq and other assays applied to a wide variety of cell types, forming a comprehensive bioinformatics resource. In this work we combine Hi-C datasets describing physical genomic contacts with a large and diverse array of chromatin features derived at a much finer scale in the same mammalian cell types. These features include levels of bound transcription factors, histone modifications and expression data. These data are then integrated in a statistically rigorous way, through a predictive modelling framework from the machine learning field. These studies were extended, within a collaborative project, to encompass a dataset of matched Hi-C and expression data collected over a murine neural differentiation timecourse. We compare higher order chromatin organisation across a variety of human cell types and find pervasive conservation of chromatin organisation at multiple scales. We also identify structurally variable regions between cell types, that are rich in active enhancers and contain loci of known cell-type specific function. We show that broad aspects of higher order chromatin organisation, such as nuclear compartment domains, can be accurately predicted in a variety of human cell types, using models based upon underlying chromatin features. We dissect these quantitative models and find them to be generalisable to novel cell types, presumably reflecting fundamental biological rules linking compartments with key activating and repressive signals. These models describe the strong interconnectedness between locus-level patterns of local histone modifications and bound factors, on the order of hundreds or thousands of basepairs, with much broader compartmentalisation of large, multi-megabase chromosomal regions. Finally, boundary regions are investigated in terms of chromatin features and co-localisation with other known nuclear structures, such as association with the nuclear lamina. We find boundary complexity to vary between cell types and link TAD aggregations to previously described lamina-associated domains, as well as exploring the concept of meta-boundaries that span multiple levels of organisation. Together these analyses lend quantitative evidence to a model of higher order genome organisation that is largely stable between cell types, but can selectively vary locally, based on the activation or repression of key loci