A resegmentation-shift model for vertebral patterning

Segmentation of the vertebrate body axis is established in the embryo by formation of somites, which give rise to the axial muscles (myotome) and vertebrae (sclerotome). To allow a muscle to attach to two successive vertebrae, the myotome and sclerotome must be repositioned by half a segment with respect to each other. Two main models have been put forward: 'resegmentation' proposes that each half-sclerotome joins with the half-sclerotome from the next adjacent somite to form a vertebra containing cells from two successive somites on each side of the midline. The second model postulates that a single vertebra is made from a single somite and that the sclerotome shifts with respect to the myotome. There is conflicting evidence for these models, and the possibility that the mechanism may vary along the vertebral column has not been considered. Here we use DiI and DiO to trace somite contributions to the vertebrae in different axial regions in the chick embryo. We demonstrate that vertebral bodies and neural arches form by resegmentation but that sclerotome cells shift in a region-specific manner according to their dorsoventral position within a segment. We propose a 'resegmentation-shift' model as the mechanism for amniote vertebral patterning

The role of the notochord in amniote vertebral column segmentation

The vertebral column is segmented, comprising an alternating series of vertebrae and intervertebral discs along the head-tail axis. The vertebrae and outer portion (annulus fibrosus) of the disc are derived from the sclerotome part of the somites, whereas the inner nucleus pulposus of the disc is derived from the notochord. Here we investigate the role of the notochord in vertebral patterning through a series of microsurgical experiments in chick embryos. Ablation of the notochord causes loss of segmentation of vertebrae and discs. However, the notochord cannot segment in the absence of the surrounding sclerotome. To test whether the notochord dictates sclerotome segmentation, we grafted an ectopic notochord. We find that the intrinsic segmentation of the sclerotome is dominant over any segmental information the notochord may possess, and no evidence that the chick notochord is intrinsically segmented. We propose that the segmental pattern of vertebral bodies and discs in chick is dictated by the sclerotome, which first signals to the notochord to ensure that the nucleus pulposus develops in register with the somite-derived annulus fibrosus. Later, the notochord is required for maintenance of sclerotome segmentation as the mature vertebral bodies and intervertebral discs form. These results highlight differences in vertebral development between amniotes and zebrafish and some other teleosts, where the notochord dictates the segmental pattern. The relative importance of the sclerotome and notochord in vertebral patterning has changed significantly during evolution

A mathematical modelling study of an athlete's sprint time when towing a weighted sled

This is the author's accepted manuscript. The final publication is available at Springer via http://dx.doi.org/10.1007/s12283-013-0114-2.This study used a mathematical model to examine the effects of the sled, the running surface, and the athlete on sprint time when towing a weighted sled. Simulations showed that ratio scaling is an appropriate method of normalising the weight of the sled for athletes of different body size. The relationship between sprint time and the weight of the sled was almost linear, as long as the sled was not excessively heavy. The athlete’s sprint time and rate of increase in sprint time were greater on running surfaces with a greater coefficient of friction, and on any given running surface an athlete with a greater power-to-weight ratio had a lower rate of increase in sprint time. The angle of the tow cord did not have a substantial effect on an athlete’s sprint time. This greater understanding should help coaches set the training intensity experienced by an athlete when performing a sled-towing exercise

Cohort profile : Oxford Pain, Activity and Lifestyle (OPAL) Study, a prospective cohort study of older adults in England

Purpose: The ‘Oxford Pain, Activity and Lifestyle’ (OPAL) Cohort is a longitudinal, prospective cohort study of adults, aged 65 years and older, living in the community which is investigating the determinants of health in later life. Our focus was on musculoskeletal pain and mobility, but the cohort is designed with flexibility to include new elements over time. This paper describes the study design, data collection and baseline characteristics of participants. We also compared the OPAL baseline characteristics with nationally representative data sources. Participants: We randomly selected eligible participants from two stratified age bands (65–74 and 75 and over years). In total, 5409 individuals (42.1% of eligible participants) from 35 general practices in England agreed to participate between 2016 and 2018. The majority of participants (n=5367) also consented for research team to access their UK National Health Service (NHS) Digital and primary healthcare records. Findings: to date Mean participant age was 74.9 years (range 65–100); 51.5% (n=2784/5409) were women. 94.9% of participants were white, and 28.8% lived alone. Over 83.0% reported pain in at least one body area in the previous 6 weeks. Musculoskeletal symptoms were more prevalent in women (86.4%). One-third of participants reported having one or more falls in the last year. Most participants were confident in their ability to walk outside. The characteristics of OPAL Cohort participants were broadly similar to the general population of the same age. Future plans: Postal follow-up of the cohort is being undertaken at annual intervals, with data collection ongoing. Linkage to NHS hospital admission data is planned. This English prospective cohort offers a large and rich resource for research on the longitudinal associations between demographic, clinical, and social factors and health trajectories and outcomes in community-dwelling older people

Atypical bodily self-awareness in vicarious pain responders

Vicarious perception refers to the ability to co-represent the experiences of others. Prior research has shown considerable inter-individual variability in vicarious perception of pain, with some experiencing conscious sensations of pain on their own body when viewing another person in pain (conscious vicarious perception / mirror-pain synaesthesia). Self-Other Theory proposes that this conscious vicarious perception may result from impairments in self-other distinction and maintaining a coherent sense of bodily self. In support of this, individuals who experience conscious vicarious perception are more susceptible to illusions of body ownership and agency. However, little work has assessed whether trait differences in bodily self-awareness are associated with conscious vicarious pain. Here we addressed this gap by examining individual difference factors related to awareness of the body, in conscious vicarious pain responders. Increased self-reported depersonalisation and interoceptive sensibility was found for conscious vicarious pain responders compared with non-responders, in addition to more internally-oriented thinking (associated with lower alexithymia). There were no significant differences in trait anxiety. Results indicate that maintaining a stable sense of the bodily self may be important for vicarious perception of pain, and that vicarious perception might also be enhanced by attention towards internal bodily states

Control over phase separation and nucleation using a laser-tweezing potential

Control over the nucleation of new phases is highly desirable but elusive. Even though there is a long history of crystallization engineering by varying physicochemical parameters, controlling which polymorph crystallizes or whether a molecule crystallizes or forms an amorphous precipitate is still a poorly understood practice. Although there are now numerous examples of control using laser-induced nucleation, the absence of physical understanding is preventing progress. Here we show that the proximity of a liquid–liquid critical point or the corresponding binodal line can be used by a laser-tweezing potential to induce concentration gradients. A simple theoretical model shows that the stored electromagnetic energy of the laser beam produces a free-energy potential that forces phase separation or triggers the nucleation of a new phase. Experiments in a liquid mixture using a low-power laser diode confirm the effect. Phase separation and nucleation using a laser-tweezing potential explains the physics behind non-photochemical laser-induced nucleation and suggests new ways of manipulating matter

Detection of chromosome aberrations in metaphase and interphase tumor cells by in situ hybridization using chromosome-specific library probes

Chromosome aberrations in two glioma cell lines were analyzed using biotinylated DNA library probes that specifically decorate chromosomes 1, 4, 7, 18 and 22 from pter to qter. Numerical changes, deletions and rearrangements of these chromosomes were radily visualized in metaphase spreads, as well as in early prophase and interphase nuclei. Complete chromosomes, deleted chromosomes and segments of translocated chromosomes were rapidly delineated in very complex karyotypes. Simultaneous hybridizations with additional subregional probes were used to further define aberrant chromosomes. Digital image analysis was used to quantitate the total complement of specific chromosomal DNAs in individual metaphase and interphase cells of each cell line. In spite of the fact that both glioma lines have been passaged in vitro for many years, an under-representation of chromosome 22 and an over-representation of chromosome 7 (specifically 7p) were observed. These observations agree with previous studies on gliomas. In addition, sequences of chromosome 4 were also found to be under-represented, especially in TC 593. These analyses indicate the power of these methods for pinpointing chromosome segments that are altered in specific types of tumors

Novel cyclic di-GMP effectors of the YajQ protein family control bacterial virulence

Bis-(3 ',5 ') cyclic di-guanylate (cyclic di-GMP) is a key bacterial second messenger that is implicated in the regulation of many critical processes that include motility, biofilm formation and virulence. Cyclic di-GMP influences diverse functions through interaction with a range of effectors. Our knowledge of these effectors and their different regulatory actions is far from complete, however. Here we have used an affinity pull-down assay using cyclic di-GMP-coupled magnetic beads to identify cyclic di-GMP binding proteins in the plant pathogen Xanthomonas campestris pv. campestris (Xcc). This analysis identified XC_3703, a protein of the YajQ family, as a potential cyclic di-GMP receptor. Isothermal titration calorimetry showed that the purified XC_3703 protein bound cyclic di-GMP with a high affinity (K-d similar to 2 mu M). Mutation of XC_3703 led to reduced virulence of Xcc to plants and alteration in biofilm formation. Yeast two-hybrid and far-western analyses showed that XC_3703 was able to interact with XC_2801, a transcription factor of the LysR family. Mutation of XC_2801 and XC_3703 had partially overlapping effects on the transcriptome of Xcc, and both affected virulence. Electromobility shift assays showed that XC_3703 positively affected the binding of XC_2801 to the promoters of target virulence genes, an effect that was reversed by cyclic di-GMP. Genetic and functional analysis of YajQ family members from the human pathogens Pseudomonas aeruginosa and Stenotrophomonas maltophilia showed that they also specifically bound cyclic di-GMP and contributed to virulence in model systems. The findings thus identify a new class of cyclic di-GMP effector that regulates bacterial virulence