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1.
bioRxiv ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38915725

RESUMO

The cardiac neural crest is critical for the normal development of the heart, as its surgical ablation in the chick recapitulates common human congenital heart defects such as 'Common Arterial Trunk' and 'Double Outlet Right Ventricle' (DORV). While left-right asymmetry is known to be important for heart development, little is known about potential asymmetric differences between right and left cardiac neural folds with respect to heart development. Here, through surgical ablation of either left or right cardiac neural crest, we reveal that right ablation results in more varied and more severe heart defects. Embryos with Common Arterial Trunk and with missing arteries occur only in right-ablated embryos; moreover, embryos with DORV and with misalignment of the arteries were more prevalent following right versus left cardiac crest ablation. In addition, overall survival of right-ablated embryos was lower than left-ablated embryos, with embryos dying earlier in development. Together, these data implicate different functions for left versus right cardiac neural crest in heart development.

2.
EMBO J ; 41(17): e108780, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35815410

RESUMO

Schwann cell precursors (SCPs) are nerve-associated progenitors that can generate myelinating and non-myelinating Schwann cells but also are multipotent like the neural crest cells from which they originate. SCPs are omnipresent along outgrowing peripheral nerves throughout the body of vertebrate embryos. By using single-cell transcriptomics to generate a gene expression atlas of the entire neural crest lineage, we show that early SCPs and late migratory crest cells have similar transcriptional profiles characterised by a multipotent "hub" state containing cells biased towards traditional neural crest fates. SCPs keep diverging from the neural crest after being primed towards terminal Schwann cells and other fates, with different subtypes residing in distinct anatomical locations. Functional experiments using CRISPR-Cas9 loss-of-function further show that knockout of the common "hub" gene Sox8 causes defects in neural crest-derived cells along peripheral nerves by facilitating differentiation of SCPs towards sympathoadrenal fates. Finally, specific tumour populations found in melanoma, neurofibroma and neuroblastoma map to different stages of SCP/Schwann cell development. Overall, SCPs resemble migrating neural crest cells that maintain multipotency and become transcriptionally primed towards distinct lineages.


Assuntos
Crista Neural , Células de Schwann , Diferenciação Celular/fisiologia , Neurogênese/fisiologia , Nervos Periféricos , Células de Schwann/metabolismo
3.
Dev Biol ; 490: 13-21, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35779606

RESUMO

The head-tail axis in birds and mammals develops from a growth zone in the tail-end, which contains the node. This growth zone then forms the tailbud. Labelling experiments have shown that while many cells leave the node and tailbud to contribute to axial (notochord, floorplate) and paraxial (somite) structures, some cells remain resident in the node and tailbud. Could these cells be resident axial stem cells? If so, do the node and tailbud represent an instructive stem cell niche that specifies and maintains these stem cells? Serial transplantation and single cell labelling studies support the existence of self-renewing stem cells and heterotopic transplantations suggest that the node can instruct such self-renewing behaviour. However, only single cell manipulations can reveal whether self-renewing behaviour occurs at the level of a cell population (asymmetric or symmetric cell divisions) or at the level of single cells (asymmetric divisions only). We combine data on resident cells in the node and tailbud and review it in the context of axial development in chick and mouse, summarising our current understanding of axial stem cells and their niche and highlighting future directions of interest.


Assuntos
Somitos , Células-Tronco , Animais , Divisão Celular , Mamíferos , Mesoderma , Camundongos , Notocorda
4.
Proc Natl Acad Sci U S A ; 119(5)2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35101917

RESUMO

In warm-blooded vertebrate embryos (mammals and birds), the axial tissues of the body form from a growth zone at the tail end, Hensen's node, which generates neural, mesodermal, and endodermal structures along the midline. While most cells only pass through this region, the node has been suggested to contain a small population of resident stem cells. However, it is unknown whether the rest of the node constitutes an instructive niche that specifies this self-renewal behavior. Here, we use heterotopic transplantation of groups and single cells and show that cells not destined to enter the node can become resident and self-renew. Long-term resident cells are restricted to the posterior part of the node and single-cell RNA-sequencing reveals that the majority of these resident cells preferentially express G2/M phase cell-cycle-related genes. These results provide strong evidence that the node functions as a niche to maintain self-renewal of axial progenitors.


Assuntos
Padronização Corporal/fisiologia , Organizadores Embrionários/fisiologia , Nicho de Células-Tronco/fisiologia , Animais , Embrião de Galinha , Endoderma/embriologia , Gástrula/embriologia , Mesoderma/embriologia , Sistema Nervoso , Notocorda/embriologia , Organizadores Embrionários/metabolismo , Nicho de Células-Tronco/genética , Células-Tronco/metabolismo , Células-Tronco/fisiologia
5.
Dev Dyn ; 251(6): 1077-1087, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34324246

RESUMO

BACKGROUND: Lissotriton vulgaris ("smooth newt") was an important organism for experimental embryology, especially in the early 20th century. The stages of development of L. vulgaris from the appearance of the first cleavage to metamorphosis have previously been described, but only through drawings. RESULTS: Referring to Glaesner's staging and utilizing a makeshift lockdown laboratory, this study documents the development of L. vulgaris embryos in a small garden pond in Surrey, UK. This study describes varying developmental rates between individuals, identifies pigmented cells in close proximity/contributing to the heart, describes early gill development and reports a case of spontaneous, non-conjoined newt twins. CONCLUSIONS: While pigmentation in the heart has been reported in some amphibians, no pigmentation within urodele hearts has been documented to date. Furthermore, although the literature on conjoined twinning in amphibia is extensive, separate, non-conjoined twinning is largely unexplored in the literature. This study invites further research into understanding of these topics.


Assuntos
Jardins , Lagoas , Animais , Humanos , Salamandridae
6.
Cells Dev ; 168: 203729, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34456178

RESUMO

Schwann cell precursors (SCPs) are a transient population in the embryo, closely associated with nerves along which they migrate into the periphery of the body. Long considered to be progenitors that only form Schwann cells-the myelinating cells of nerves, current evidence suggests that SCPs have much broader developmental potential. Indeed, different cell marking techniques employed over the past 20 years have identified multiple novel SCP derivatives throughout the body. It is now clear that SCPs represent a multipotent progenitor population, which also display a level of plasticity in response to injury. Moreover, they originate from multiple origins in the embryo and may reflect several distinct subpopulations in terms of molecular identity and fate. Here we review SCP origins, derivatives and plasticity in development, growth and repair.


Assuntos
Embrião de Mamíferos , Células de Schwann , Diferenciação Celular/fisiologia , Células de Schwann/fisiologia
7.
Cells Dev ; 166: 203686, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33994354

RESUMO

Schwann cell precursors (SCPs) are a transient population in the embryo, closely associated with nerves along which they migrate into the periphery of the body. Long considered to be progenitors that only form Schwann cells-the myelinating cells of nerves, current evidence suggests that SCPs have much broader developmental potential. Indeed, different cell marking techniques employed over the past 20 years have identified multiple novel SCP derivatives throughout the body. It is now clear that SCPs represent a multipotent progenitor population, which also display a level of plasticity in response to injury. Moreover, they originate from multiple origins in the embryo and may reflect several distinct subpopulations in terms of molecular identity and fate. Here we review SCP origins, derivatives and plasticity in development, growth and repair.


Assuntos
Células de Schwann/citologia , Células-Tronco/citologia , Animais , Diferenciação Celular , Linhagem da Célula , Humanos , Modelos Biológicos , Plasticidade Neuronal
8.
Nat Commun ; 7: 12656, 2016 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-27557800

RESUMO

Organizers are regions of the embryo that can both induce new fates and impart pattern on other regions. So far, surprisingly few organizers have been discovered, considering the number of patterned tissue types generated during development. This may be because their discovery has relied on transplantation and ablation experiments. Here we describe a new approach, using chick embryos, to discover organizers based on a common gene expression signature, and use it to uncover the anterior intestinal portal (AIP) endoderm as a putative heart organizer. We show that the AIP can induce cardiac identity from non-cardiac mesoderm and that it can pattern this by specifying ventricular and suppressing atrial regional identity. We also uncover some of the signals responsible. The method holds promise as a tool to discover other novel organizers acting during development.


Assuntos
Coração/embriologia , Organizadores Embrionários/metabolismo , Animais , Biomarcadores/metabolismo , Padronização Corporal , Galinhas , Endoderma/embriologia , Endoderma/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Átrios do Coração/embriologia , Átrios do Coração/metabolismo , Ventrículos do Coração/embriologia , Ventrículos do Coração/metabolismo , Mucosa Intestinal/metabolismo , Intestinos/embriologia , Mesoderma/embriologia , Mesoderma/metabolismo , Modelos Biológicos , Codorniz , Transcriptoma/genética
9.
W V Med J ; 108(6): 12-7, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23472535

RESUMO

Five realistic tabletop scenarios were designed to facilitate threat preparedness training of Medical, Public Health, Nursing, Emergency Services, Mental Health, Allied Health, and Pharmacy personnel. Training scenarios were (1) student contaminates lettuce (Act) in a state university with Shigella sonnei (Agent), (2) dismissed athlete contaminates ice (Act) at the basketball tournament with Escherichia coli (Agent), (3) workers fail to report abandoned backpacks (Act) at a state fair that contain smallpox virus (Agent), (4) terrorists expose county residents (Act) to Pneumonic plague bacterium (Agent), and (5) infected birds expose field-trip participants (Act) to Avian influenza virus (Agent). Evaluation of the tabletops yielded positive ratings of educational outcomes in these domains: well-structured, organized, plausible, realistic, engaging, on-target, useful, and multidisciplinary. Attendees with previous blended-learning courses on bioterrorism and threat preparedness enhanced performance in the tabletop exercises. Evaluative data indicated a new level of competence and self-confidence about being part of a coordinated, local-level, interdisciplinary response.


Assuntos
Defesa Civil/educação , Planejamento em Desastres/métodos , Bioterrorismo , Humanos , Prática Psicológica
10.
Disabil Health J ; 4(4): 201-8, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22014667

RESUMO

BACKGROUND: Personal assistance services (PAS) can be valuable adjuncts to the complement of accommodations that support workers with disabilities. This literature review explored the professional literature on the use of PAS in the workplace. METHODS: Bibliographic sources were used to locate relevant research studies on the use of PAS in the workplace. The studies in this review used both qualitative and quantitative methods to identify current definitions of work-related and personal care-related PAS, agency-directed versus consumer-directed PAS, long-term and short-term funding issues, development of PAS policy, and barriers to successful implementation of PAS. RESULTS: The studies uncovered issues related to (a) recruiting, training, and retaining personal assistants, (b) employer concerns, (c) costs and benefits of workplace PAS, (d) wages and incentives for personal assistants, and (e) sources for financing PAS as a workplace accommodation. CONCLUSION: The findings reveal the value and benefits of effective PAS on the job. PAS can lead to successful employment of people with disabilities when other accommodations cannot provide adequate workplace support. Additionally, the evolution of workplace PAS is dependent on development of realistic PAS policy and funding options.


Assuntos
Pessoas com Deficiência , Serviços de Saúde do Trabalhador , Local de Trabalho , Emprego , Humanos
11.
Disabil Health J ; 4(1): 39-45, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21168806

RESUMO

BACKGROUND: This study explored workplace disability accommodations and their benefits. The participants were employers and human resource professionals who had not used the services of the Job Accommodation Network (JAN). The companies included large businesses (more than 499 employees) and small businesses (fewer than 500 employees). OBJECTIVE/HYPOTHESIS: The intent of this investigation was to assess the disability accommodations and benefits for the employers. METHODS: The study used responses to online survey from194 employers to discuss disability-related accommodations for an employee or potential employee. The survey included 128 employers who reported having had a person with a disability who requested an accommodation. RESULTS: As reported by the employers, the most frequently mentioned direct benefits from implementing workplace accommodations were (a) retained a qualified employee, (b) increased worker productivity, and (c) eliminated the cost of training a new employee. The most frequently mentioned indirect benefits from accommodations were (a) improved interactions with coworkers, (b) increased overall company morale, and (c) increased overall company productivity. The most frequently reported types of implemented accommodations were buying equipment and changing work schedules. Most of the respondents estimated the direct benefits of having made an accommodation at more than $1000. CONCLUSIONS: The findings heighten awareness of benefits associated with making accommodations for people with disabilities in the workplace. These benefits signify value for business, coworkers, and individuals with disabilities for whom accommodations are critical for successful employment.


Assuntos
Comércio , Pessoas com Deficiência , Readaptação ao Emprego , Local de Trabalho , Adolescente , Adulto , Idoso , Coleta de Dados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
12.
Work ; 36(3): 339-43, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20683168

RESUMO

OBJECTIVE: The intent of this investigation was to identify current definitions, issues, and strategies related to the use of Personal Assistance Services (PAS) in the workplace. PARTICIPANTS: The participants were employees with disabilities who used PAS in the workplace as well as employers who participated in research studies over the past 20 years. METHODS: More than 30 articles were reviewed to determine PAS definitions, use, policies, and outcomes. A comprehensive search of bibliographic resources (e.g., EBSCOhost) was conducted to identify appropriate articles. RESULTS: The articles revealed current definitions of workplace PAS, demonstrated an increasing need for PAS, and highlighted fiscal and societal barriers to the full implementation of PAS at work. CONCLUSIONS: The outcomes clarify the historical components, but also identify questions that remain. These questions concern the effectiveness of PAS, best practices for funding PAS, and the need for national and local policies to support the use of PAS for workers with disabilities.


Assuntos
Pessoas com Deficiência , Assistência Individualizada de Saúde , Autocuidado , Atividades Cotidianas , Emprego , Humanos , Local de Trabalho
13.
Disabil Health J ; 2(4): 196-205, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21122760

RESUMO

BACKGROUND: This study compared the expense associated with use of personal assistance services (PAS) for individuals with disabilities to the expense incurred by individuals with disabilities who did not use PAS. The intent of this investigation was to assess the disability accommodation costs and benefits of PAS and non-PAS cases. METHODS: The study uses 1,182 follow-up telephone surveys and 24 telephone interviews of employers who had previously contacted the Job Accommodation Network (JAN) to discuss disability-related accommodations for an employee or potential employee that were conducted from January 2004 through December 2006. The survey included 69 employers who had considered PAS. The surveys were conducted by the University of Iowa's Law, Health Policy, and Disability Center, which contacted employers who had previously contacted JAN for consultation on workplace accommodations. The interviews were conducted by the International Center for Disability Information at West Virginia University. RESULTS: Key findings point to the costs associated with PAS cases and with cases not involving PAS accommodations. As reported by the employers, the median "one-time cost" of accommodations (not $0) for non-PAS cases was $500. The median "one-time cost" of accommodations (not $0) for PAS cases was $1,850. When $0 cost of accommodations on PAS cases was factored in with "one-time cost" of accommodations for PAS cases, the median cost was $0. For non-PAS cases of accommodations, when $0 cost of accommodations was considered, the outcome was a median cost of $0. The annual cost for PAS accommodations was a median cost of $8,000 in comparison to $2,000 for non-PAS. The median dollar amount estimates of direct benefits were $1,600 for PAS accommodations, similar to $1,500 for non-PAS. The most frequently mentioned benefits from PAS accommodations were (a) increased productivity, (b) increased diversity, (c) retention of a valued employee, (d) improved interactions with co-workers, (e) increased overall company morale, and (f) increased overall company productivity. CONCLUSIONS: The findings heighten awareness of the cost and benefits aspects associated with PAS for people with disabilities. Many non-PAS accommodations cost nothing to the employer (e.g., changing the work schedule, moving the individual to another location). When dollar cost was involved, the costs for PAS accommodations were more than three times greater than non-PAS accommodations.


Assuntos
Pessoas com Deficiência , Readaptação ao Emprego/economia , Gastos em Saúde , Assistência Individualizada de Saúde/economia , Local de Trabalho/economia , Análise Custo-Benefício , Pesquisas sobre Atenção à Saúde , Humanos , Entrevistas como Assunto , Iowa , West Virginia
14.
J Rural Health ; 21(3): 206-13, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16092293

RESUMO

CONTEXT: Many rural elders experience limited access to health care. The majority of what we know about this issue has been based upon quantitative studies, yet qualitative studies might offer additional insight into individual perceptions of health care access. PURPOSE: To examine what barriers rural elders report when accessing needed health care, including how they cope with the high cost of prescription medication. METHODS: During Spring 2001, thirteen 90-minute focus groups were conducted in 6 rural West Virginia communities. A total of 101 participants, aged 60 years and older, were asked several culminating questions about their perceptions of health care access. FINDINGS: Five categories of barriers to health care emerged from the discussions: transportation difficulties, limited health care supply, lack of quality health care, social isolation, and financial constraints. In addition, 6 diverse coping strategies for dealing with the cost of prescription medication were discussed. They included: reducing dosage or doing without, limiting other expenses, relying on family assistance, supplementing with alternative medicine, shopping around for cheapest prices, and using the Veteran's Administration. CONCLUSIONS: Overall, rural older adults encounter various barriers to accessing needed health care. Qualitative methodology allows rural elders to have a voice to expound on their experiences. Research can contribute valuable information to shape policy by providing a forum where older adults can express their concerns about the current health care delivery system.


Assuntos
Acessibilidade aos Serviços de Saúde , Serviços de Saúde para Idosos/estatística & dados numéricos , Satisfação do Paciente , Serviços de Saúde Rural/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Prescrições de Medicamentos/economia , Feminino , Financiamento Pessoal , Grupos Focais , Serviços de Saúde para Idosos/normas , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Relações Médico-Paciente , Qualidade da Assistência à Saúde , Serviços de Saúde Rural/normas , Classe Social , Isolamento Social , Meios de Transporte , West Virginia
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