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"Williams, Ruth M"
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Positive Psychology Interventions in Practice
\"This book presents recent advancements in positive psychology, specifically its application across broad areas of current interest. Chapters include submissions from various international authors in the field and cover discussion and presentation of relevant research, theories, and applications. The volume covers topics such as CBT, Psychotherapy, Coaching, Workplaces, Aging, Education, Leadership, Emotion, Interventions, Measurement, Technology, Design, Health, Relationships, Experiences, Communities. With the growing interest in the applications of positive psychology across diverse fields within psychology and beyond, this book will make a worthwhile contribution to the field. It will also fill the current need for a volume that highlights specifically the various recent advancements in positive psychology into diverse fields and as such will be of benefit to a wide range of professionals, including psychologists, educators, clinicians, therapists, and many others.\" -- Publisher's website.
Book
A genome-wide assessment of the ancestral neural crest gene regulatory network
The neural crest (NC) is an embryonic cell population that contributes to key vertebrate-specific features including the craniofacial skeleton and peripheral nervous system. Here we examine the transcriptional and epigenomic profiles of NC cells in the sea lamprey, in order to gain insight into the ancestral state of the NC gene regulatory network (GRN). Transcriptome analyses identify clusters of co-regulated genes during NC specification and migration that show high conservation across vertebrates but also identify transcription factors (TFs) and cell-adhesion molecules not previously implicated in NC migration. ATAC-seq analysis uncovers an ensemble of
cis
-regulatory elements, including enhancers of
Tfap2B, SoxE1
and
Hox-
α
2 validated in the embryo. Cross-species deployment of lamprey elements identifies the deep conservation of lamprey
SoxE1
enhancer activity, mediating homologous expression in jawed vertebrates. Our data provide insight into the core GRN elements conserved to the base of the vertebrates and expose others that are unique to lampreys.
An understanding of the ancestral state of the neural crest (NC) gene regulatory network (GRN) gives insight into vertebrate evolution. Here, the authors use transcriptomic and chromatin accessibility analyses of the lamprey NC, as well as cross-species enhancer assays, to identify GRN elements conserved throughout vertebrates.
Journal Article
Single-cell atlas of early chick development reveals gradual segregation of neural crest lineage from the neural plate border during neurulation
The epiblast of vertebrate embryos is comprised of neural and non-neural ectoderm, with the border territory at their intersection harboring neural crest and cranial placode progenitors. Here, we a generate single-cell atlas of the developing chick epiblast from late gastrulation through early neurulation stages to define transcriptional changes in the emerging ‘neural plate border’ as well as other regions of the epiblast. Focusing on the border territory, the results reveal gradual establishment of heterogeneous neural plate border signatures, including novel genes that we validate by fluorescent in situ hybridization. Developmental trajectory analysis infers that segregation of neural plate border lineages only commences at early neurulation, rather than at gastrulation as previously predicted. We find that cells expressing the prospective neural crest marker Pax7 contribute to multiple lineages, and a subset of premigratory neural crest cells shares a transcriptional signature with their border precursors. Together, our results suggest that cells at the neural plate border remain heterogeneous until early neurulation, at which time progenitors become progressively allocated toward defined neural crest and placode lineages. The data also can be mined to reveal changes throughout the developing epiblast.
Journal Article
Characterising open chromatin in chick embryos identifies cis-regulatory elements important for paraxial mesoderm formation and axis extension
Somites arising from paraxial mesoderm are a hallmark of the segmented vertebrate body plan. They form sequentially during axis extension and generate musculoskeletal cell lineages. How paraxial mesoderm becomes regionalised along the axis and how this correlates with dynamic changes of chromatin accessibility and the transcriptome remains unknown. Here, we report a spatiotemporal series of ATAC-seq and RNA-seq along the chick embryonic axis. Footprint analysis shows differential coverage of binding sites for several key transcription factors, including CDX2, LEF1 and members of
HOX
clusters. Associating accessible chromatin with nearby expressed genes identifies cis-regulatory elements (CRE) for
TCF15
and
MEOX1
. We determine their spatiotemporal activity and evolutionary conservation in Xenopus and human. Epigenome silencing of endogenous CREs disrupts
TCF15
and
MEOX1
gene expression and recapitulates phenotypic abnormalities of anterior–posterior axis extension. Our integrated approach allows dissection of paraxial mesoderm regulatory circuits in vivo and has implications for investigating gene regulatory networks.
How paraxial mesoderm formation and differentiation is regulated is unclear. Here, the authors identify accessible chromatin and gene expression signatures that define different stages of paraxial mesoderm development in the chick and identify CREs important for vertebrate anterior–posterior axis formation.
Journal Article
A functional approach to understanding the role of NCKX5 in Xenopus pigmentation
NCKX5 is an ion exchanger expressed mostly in pigment cells; however, the functional role for this protein in melanogenesis is not clear. A variant allele of SLC24A5, the gene encoding NCKX5, has been shown to correlate with lighter skin pigmentation in humans, indicating a key role for SLC24A5 in determining human skin colour. SLC24A5 expression has been found to be elevated in melanoma. Knockdown analyses have shown SLC24A5 to be important for pigmentation, but to date the function of this ion exchanger in melanogenesis has not been fully established. Our data suggest NCKX5 may have an alternative activity that is key to its role in the regulation of pigmentation. Here Xenopus laevis is employed as an in vivo model system to further investigate the function of NCKX5 in pigmentation. SLC24A5 is expressed in the melanophores as they differentiate from the neural crest and develop in the RPE of the eye. Morpholino knockdown and rescue experiments were designed to elucidate key residues and regions of the NCKX5 protein. Unilateral morpholino injection at the 2 cell stage resulted in a reduction of pigmentation in the eye and epidermis of one lateral side of the tadpole. Xenopus and human SLC24A5 can rescue the morpholino effects. Further rescue experiments including the use of ion exchange inactive SLC24A5 constructs raise the possibility that full ion exchanger function of NCKX5 may not be required for rescue of pigmentation.
Journal Article
Macrophages directly contribute collagen to scar formation during zebrafish heart regeneration and mouse heart repair
Canonical roles for macrophages in mediating the fibrotic response after a heart attack include extracellular matrix turnover and activation of cardiac fibroblasts to initiate collagen deposition. Here we reveal that macrophages directly contribute collagen to the forming post-injury scar. Unbiased transcriptomics shows an upregulation of collagens in both zebrafish and mouse macrophages following heart injury. Adoptive transfer of macrophages, from either collagen-tagged zebrafish or adult mouse GFP
tpz
-collagen donors, enhances scar formation via cell autonomous production of collagen. In zebrafish, the majority of tagged collagen localises proximal to the injury, within the overlying epicardial region, suggesting a possible distinction between macrophage-deposited collagen and that predominantly laid-down by myofibroblasts. Macrophage-specific targeting of
col4a3bpa
and cognate
col4a1
in zebrafish significantly reduces scarring in cryoinjured hosts. Our findings contrast with the current model of scarring, whereby collagen deposition is exclusively attributed to myofibroblasts, and implicate macrophages as direct contributors to fibrosis during heart repair.
Macrophages mediate the fibrotic response after a heart attack by extracellular matrix turnover and cardiac fibroblasts activation. Here the authors identify an evolutionarily-conserved function of macrophages that contributes directly to the forming post-injury scar through cell-autonomous deposition of collagen.
Journal Article
Chromatin remodeller Chd7 is developmentally regulated in the neural crest by tissue-specific transcription factors
Neurocristopathies such as CHARGE syndrome result from aberrant neural crest development. A large proportion of CHARGE cases are attributed to pathogenic variants in the gene encoding CHD7, chromodomain helicase DNA binding protein 7, which remodels chromatin. While the role for CHD7 in neural crest development is well documented, how this factor is specifically up-regulated in neural crest cells is not understood. Here, we use epigenomic profiling of chick and human neural crest to identify a cohort of enhancers regulating Chd7 expression in neural crest cells and other tissues. We functionally validate upstream transcription factor binding at candidate enhancers, revealing novel epistatic relationships between neural crest master regulators and Chd7, showing tissue-specific regulation of a globally acting chromatin remodeller. Furthermore, we find conserved enhancer features in human embryonic epigenomic data and validate the activity of the human equivalent CHD7 enhancers in the chick embryo. Our findings embed Chd7 in the neural crest gene regulatory network and offer potentially clinically relevant elements for interpreting CHARGE syndrome cases without causative allocation.
Journal Article
Discrete quantum gravity
A review is given of a number of approaches to discrete quantum gravity, with a restriction to those likely to be relevant in four dimensions. This paper is dedicated to Rafael Sorkin on the occasion of his sixtieth birthday.
Journal Article
A study of attendance and filling in of pre-appointment questionnaires in an outpatient clinical psychology service
This study looked at whether filling in pre-appointment questionnaires was related to attendance in an adult clinical psychology out-patient service. Comparisons were made between attenders who filled in forms, attenders who did not fill in forms, non-attenders who filled in forms and non-attenders who did not fill in forms. The variables compared were: age, source of referral, reason for referral, gender, Health Authority, ethnic origin, marital status, level of anxiety (BAI), level of depression (BDI) and severity of symptoms (SCL-90). Attendance was much higher in those who filled in pre-appointment questionnaires (75% v. 35%). In addition, non-attenders who filled in questionnaires were younger than most of the other groups; attendance rates were raised with consultant referrals; GP referred clients were less likely to fill in questionnaires; and, among form fillers, non-attenders were more likely to be single. The results are discussed with reference to their service implications.
Journal Article
Double-stranded DNA in exosomes： a novel biomarker in cancer detection
Exosomes, small membrane vesicles （30-100 nm） of endocytic origin secreted by most cell types, contain functional biomolecules, which can be horizontally transferred to recipient cells [1]. Exosomes bear a specific protein and lipid composition, and carry a select set of functional mRNAs and microRNAs [2]. Recently, our group has shown that c-Met shed in exosomes can promote a proangiogenic and prometastatic phenotype in bone marrow-derived progenitor cells during melanoma progression [3]. In previous research, retrotransposon RNA transcripts, single-stranded DNA （ssDNA）,
Journal Article