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1.
J Bone Miner Res ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38959852

RESUMO

Intracellular phosphoinositide 3-kinase (PI3K) signaling is activated by multiple bone-active receptors. Genetic mutations activating PI3K signaling are associated with clinical syndromes of tissue overgrowth in multiple organs, often including the skeleton. Bone formation is increased by removing the PI3K inhibitor PTEN, but the effect of direct PI3K in the osteoblast lineage has not been reported. We introduced a known gain-of-function mutation in Pik3ca, the gene encoding the p110α catalytic subunit of PI3K, in osteocytes and late osteoblasts using the dentin matrix protein-1 Cre (Dmp1Cre) mouse and assessed the skeletal phenotype. Femur shape was grossly normal, but cortical thickness was significantly greater in both male and female Dmp1Cre.Pik3caH1047R mice, leading to almost doubled bone strength at 12 weeks of age. Both sexes had smaller marrow areas from 6 weeks of age. Female mice also exhibited greater cross sectional area, which continued to increase until 24 weeks of age, resulting in a further increase in bone strength. While both male and female mice had increased endocortical mineralizing surface, only female mice had increased periosteal mineralizing surface. The bone formed in the Dmp1Cre.Pik3caH1047R mice showed no increase in intracortical remodeling nor any defect in cortical bone consolidation. In contrast, on both endocortical and periosteal surfaces, there was a greater extent of lamellar bone formation with highly organized osteocyte networks extending along the entire surface at a greater thickness than in control mice. In conclusion, direct activation of PI3Kα in cells targeted by Dmp1Cre leads to high cortical bone mass and strength with abundant lamellar cortical bone in female and male mice with no increase in intracortical remodeling. This differs from the effect of PTEN deletion in the same cells, suggesting that activating PI3Kα in osteoblasts and osteocytes may be a more suitable target to promote formation of lamellar bone.


Patients with genetic activation of an enzyme called phosphoinositide-3 kinase (PI3K) have tissue overgrowth syndromes, where parts of the body become enlarged, sometimes including the skeleton. There are two types of mutations that cause these problems: one that directly causes the PI3K enzyme to be more active, or one that removes the normal brake on PI3K signaling (called PTEN). We studied the effect of directly activating PI3K enzyme specifically in osteoblasts (the cells that form bone) and osteocytes (osteoblasts that make a network inside the bone tissue itself). We found mice with these mutations formed normally shaped bones that were very strong because the outer shell was thicker than usual. In both male and female mice, it became thicker on the inside of the shell, but in female mice it also became thicker on the outside, making the bones even stronger over time. The new bone was well-organized bone, which likely helped make the increase in bone strength so profound. This is very different to what has previously been shown in mice with the other type of mutation in their bone forming cells; those mice had a shell that contained many large holes (pores). This indicates that directly stimulating PI3K enzyme is more beneficial for bone than removing the PTEN brake.

2.
Nat Genet ; 54(12): 1839-1852, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36229674

RESUMO

Cancer genetics has uncovered many tumor-suppressor and oncogenic pathways, but few alterations have revealed mechanisms involved in tumor spreading. Here, we examined the role of the third most significant chromosomal deletion in human melanoma that inactivates the adherens junction gene NECTIN1 in 55% of cases. We found that NECTIN1 loss stimulates melanoma cell migration in vitro and spreading in vivo in both zebrafish and human tumors specifically in response to decreased IGF1 signaling. In human melanoma biopsy specimens, adherens junctions were seen exclusively in areas with low IGF1 levels, but not in NECTIN1-deficient tumors. Our study establishes NECTIN1 as a major determinant of melanoma dissemination and uncovers a genetic control of the response to microenvironmental signals.


Assuntos
Melanoma , Peixe-Zebra , Humanos , Animais , Peixe-Zebra/genética , Melanoma/genética , Fator de Crescimento Insulin-Like I/genética
3.
PLoS One ; 17(7): e0270799, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35797371

RESUMO

Pollen grains are male gametophytes, an ephemeral haploid generation of plants, that commonly engage in competition for a limited supply of ovules. Since variation in reproductive capabilities among male gametophytes may influence the direction and pace of evolution in populations, we must be able to quantify the relative fitness of gametophytes from different sires. To explore this, we estimated the relative fitness of groups of male gametophytes in a dioecious, wind-pollinated model system, Cannabis sativa, by characterizing the non-abortion rate (measured via chemical staining) and viability (measured via in vitro germination) of pollen from multiple sires. Pollen viability quickly declined within two weeks of anther dehiscence, and pollen stored under freezer conditions did not germinate regardless of storage time. In contrast, pollen non-abortion rates declined slowly and persisted longer than the lifetime of a sporophyte plant under both room temperature and freezer conditions. Pollen samples that underwent both viability and non-abortion rate analysis displayed no significant correlation, implying that researchers cannot predict pollen viability from non-abortion rates, nor infer male gametophytic fitness from a single measure. Our work demonstrates two independent, differential approaches to measure proxies of male fitness in C. sativa.


Assuntos
Cannabis , Células Germinativas Vegetais , Óvulo Vegetal , Plantas , Pólen
4.
Elife ; 102021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33527896

RESUMO

Recent genomic and scRNA-seq analyses of melanoma demonstrated a lack of recurrent genetic drivers of metastasis, while identifying common transcriptional states correlating with invasion or drug resistance. To test whether transcriptional adaptation can drive melanoma progression, we made use of a zebrafish mitfa:BRAFV600E;tp53-/- model, in which malignant progression is characterized by minimal genetic evolution. We undertook an overexpression-screen of 80 epigenetic/transcriptional regulators and found neural crest-mesenchyme developmental regulator SATB2 to accelerate aggressive melanoma development. Its overexpression induces invadopodia formation and invasion in zebrafish tumors and human melanoma cell lines. SATB2 binds and activates neural crest-regulators, including pdgfab and snai2. The transcriptional program induced by SATB2 overlaps with known MITFlowAXLhigh and AQP1+NGFR1high drug-resistant states and functionally drives enhanced tumor propagation and resistance to Vemurafenib in vivo. In summary, we show that melanoma transcriptional rewiring by SATB2 to a neural crest mesenchyme-like program can drive invasion and drug resistance in autochthonous tumors.


Assuntos
Resistencia a Medicamentos Antineoplásicos/genética , Proteínas de Ligação à Região de Interação com a Matriz/metabolismo , Melanoma/genética , Invasividade Neoplásica/genética , Fatores de Transcrição/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Animais , Sistemas CRISPR-Cas , Linhagem Celular Tumoral , Modelos Animais de Doenças , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas de Ligação à Região de Interação com a Matriz/genética , Melanoma/tratamento farmacológico , Melanoma/metabolismo , Crista Neural/citologia , Fatores de Transcrição/genética , Peixe-Zebra , Proteínas de Peixe-Zebra/genética
5.
Front Plant Sci ; 12: 797425, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35082815

RESUMO

Cannabis sativa L. is an annual, short-day plant, such that long-day lighting promotes vegetative growth while short-day lighting induces flowering. To date, there has been no substantial investigation on how the switch between these photoperiods influences yield of C. sativa despite the tight correlation that plant size and floral biomass have with the timing of photoperiod switches in indoor growing facilities worldwide. Moreover, there are only casual predictions around how the timing of the photoperiodic switch may affect the production of secondary metabolites, like cannabinoids. Here we use a meta-analytic approach to determine when growers should switch photoperiods to optimize C. sativa floral biomass and cannabinoid content. To this end, we searched through ISI Web of Science for peer-reviewed publications of C. sativa that reported experimental photoperiod durations and results containing cannabinoid concentrations and/or floral biomass, then from 26 studies, we estimated the relationship between photoperiod and yield using quantile regression. Floral biomass was maximized when the long daylength photoperiod was minimized (i.e., 14 days), while THC and CBD potency was maximized under long day length photoperiod for ~42 and 49-50 days, respectively. Our work reveals a yield trade-off in C. sativa between cannabinoid concentration and floral biomass where more time spent under long-day lighting maximizes cannabinoid content and less time spent under long-day lighting maximizes floral biomass. Growers should carefully consider the length of long-day lighting exposure as it can be used as a tool to maximize desired yield outcomes.

6.
Int J Mol Sci ; 21(22)2020 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-33233466

RESUMO

Studies have estimated that currently 344 million people worldwide and 16.4 million adults in the US have some form of dry eye disease (DED). It is believed that approximately 70% of DED cases are due to some form of evaporative dry eye, for which Meibomian gland dysfunction (MGD) is the major cause. Unfortunately, currently there is no effective treatment for MGD, and solely palliative care is available. Given the importance of MGD in DED, there has been a growing interest in studying Meibomian gland development, homeostasis and pathology, and, also, in developing therapies for treating and/or preventing MGD. For such, animal models have shown to be a vital tool. Much of what is known today about the Meibomian gland and MGD was learnt from these important animal models. In particular, canine and rabbit models have been essential for studying the physiopathology and progression of DED, and the mouse model, which includes different knockout strains, has enabled the identification of specific pathways potentially involved in MGD. Herein, we provide a bibliographic review on the various animal models that have been used to study Meibomian gland development, Meibomian gland homeostasis and MGD, primarily focusing on publications between 2000 and 2020.


Assuntos
Síndromes do Olho Seco/genética , Disfunção da Glândula Tarsal/genética , Glândulas Tarsais/patologia , Animais , Modelos Animais de Doenças , Cães , Síndromes do Olho Seco/patologia , Humanos , Disfunção da Glândula Tarsal/patologia , Glândulas Tarsais/metabolismo , Camundongos , Coelhos , Lágrimas/metabolismo
7.
Compr Child Adolesc Nurs ; 42(3): 222-240, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29902090

RESUMO

The purpose of this study was to conduct a youth participatory action research project to address the disparities in sexually transmitted infection (STI) and HIV rates among homeless youth. Four youth served as co-investigators and cultural informants for the project. The team conducted focus groups (N = 22; ages 16-22) and in-depth interviews (N = 20; ages 18-24) with homeless youth to explore decisions about condomless sex, knowledge of STIs and HIV, health-care access for STI-related services, and perceptions about STI testing. Findings revealed that homeless youth have good general knowledge about STIs, are receptive to STI testing for themselves and their sexual partners, and have heightened concerns about being HIV positive and peers knowing their STI status. Results from the current study could contribute to the development of youth-informed tailored interventions to increase protective sexual behavior, reduce health disparities, and improve access to and the quality of health-care services for homeless youth.


Assuntos
Infecções por HIV/terapia , Promoção da Saúde/métodos , Jovens em Situação de Rua/psicologia , Participação do Paciente/métodos , Infecções Sexualmente Transmissíveis/terapia , Adolescente , California , Feminino , Grupos Focais/métodos , Infecções por HIV/prevenção & controle , Infecções por HIV/psicologia , Humanos , Entrevistas como Assunto/métodos , Masculino , Participação do Paciente/estatística & dados numéricos , Pesquisa Qualitativa , Infecções Sexualmente Transmissíveis/prevenção & controle , Infecções Sexualmente Transmissíveis/psicologia , Adulto Jovem
8.
Dev Biol ; 449(2): 107-114, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-29883661

RESUMO

NRAS mutations are frequently found in many deadly malignancies and are the second most common oncogene driving malignant melanoma. Here, we generate a rapid transient transgenic zebrafish model of NRASQ61R-mutant melanoma. These fish develop extensive melanocytic proliferation in approximately 4 weeks. The majority of these lesions do not engraft upon transplantation and lack overt histologic features of malignancy. Our previous work demonstrated that activation of a neural crest cell transcriptional program is a key initiating event in zebrafish BRAF/p53-driven melanomas using the fluorescent reporter crestin:EGFP. By 8-12 weeks of age, some lesions progress to malignant melanoma and have cytologic atypia, destructive tissue invasion, and express neural crest progenitor markers, including crestin:EGFP. Our studies demonstrate that NRASQ61R induces extensive melanocyte expansion, which arise during zebrafish development and lack a transformed phenotype. These early lesions are highly predisposed to reactivate a neural crest progenitor fate and form malignant melanomas.


Assuntos
Proliferação de Células/genética , Genes ras/genética , Melanócitos/metabolismo , Melanoma/genética , Mutação , Crista Neural/metabolismo , Neoplasias Cutâneas/genética , Animais , Animais Geneticamente Modificados , Modelos Animais de Doenças , GTP Fosfo-Hidrolases/genética , GTP Fosfo-Hidrolases/metabolismo , Humanos , Estimativa de Kaplan-Meier , Melanócitos/patologia , Melanoma/metabolismo , Melanoma/patologia , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Fatores de Tempo , Peixe-Zebra , Melanoma Maligno Cutâneo
9.
J Nurs Educ ; 57(4): 245-249, 2018 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-29614196

RESUMO

BACKGROUND: As nursing programs continue to expand online, innovative pedagogies that support online teaching and learning practices grounded in theoretical constructs are needed. METHOD: Video simulation scenarios and VoiceThread technology were used to create a model of online instruction that promotes active student participation and aligns with course objectives and content. Kolb's experiential learning theory serves as the framework for this project. RESULTS: The integration of multimedia in the course gave students a collaborative experience where they can apply their knowledge to the simulation scenarios. Inclusion of the vignettes was found to be effective in addressing specific areas of curriculum while stimulating student engagement. CONCLUSION: Increased use of online delivery for nursing education necessitates course designs that promote student interaction and foster community. Teaching and learning practices that include technologies and are supported by theoretical constructs promote best practices for online instruction. [J Nurs Educ. 2018;57(4):245-249.].


Assuntos
Instrução por Computador , Educação em Enfermagem/organização & administração , Treinamento por Simulação/métodos , Estudantes de Enfermagem/psicologia , Gravação em Vídeo , Currículo , Difusão de Inovações , Humanos , Modelos Educacionais , Pesquisa em Educação em Enfermagem , Pesquisa em Avaliação de Enfermagem , Pesquisa Metodológica em Enfermagem , Aprendizagem Baseada em Problemas
10.
J Endod ; 42(11): 1641-1646, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27637460

RESUMO

INTRODUCTION: Surgical interventions such as tooth extraction increase the chances of developing osteonecrosis of the jaw in patients receiving bisphosphonates (BPs) for the treatment of bone-related diseases. Tooth extraction is often performed to eliminate preexisting pathological inflammatory conditions that make the tooth unsalvageable; however, the role of such conditions on bisphosphonate-related osteonecrosis of the jaw (BRONJ) development after tooth extraction is not clearly defined. Here, we examined the effects of periapical periodontitis on tooth extraction-induced BRONJ development in mice. METHODS: Periapical periodontitis was induced by exposing the pulp of the maxillary first molar for 3 weeks in C57/BL6 mice that were intravenously administered with BPs. The same tooth was extracted, and after an 3 additional weeks, the mice were harvested for histologic, histomorphometric, and histochemical staining analyses. RESULTS: Pulp exposure induced periapical radiolucency as shown by increased inflammatory cells, tartrate-resistant acid phosphatase-positive osteoclasts, and bone resorption. When BPs were administered, pulp exposure did not induce apical bone resorption despite the presence of inflammatory cells and tartrate-resistant acid phosphatase-positive osteoclasts. Although tooth extraction alone induced BRONJ lesions, pulp exposure further increased tooth extraction-induced BRONJ development as shown by the presence of more bone necrosis. CONCLUSIONS: Our study demonstrates that a preexisting pathological inflammatory condition such as periapical periodontitis is a predisposing factor that may exacerbate BRONJ development after tooth extraction. Our study further provides a clinical implication wherein periapical periodontitis should be controlled before performing tooth extraction in BP users in order to reduce the risk of developing BRONJ.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/patologia , Periodontite Periapical/patologia , Extração Dentária/efeitos adversos , Administração Intravenosa , Animais , Reabsorção Óssea/dietoterapia , Reabsorção Óssea/etiologia , Reabsorção Óssea/patologia , Difosfonatos/efeitos adversos , Modelos Animais de Doenças , Feminino , Inflamação/patologia , Maxila/patologia , Camundongos , Camundongos Endogâmicos C57BL , Dente Molar/efeitos dos fármacos , Dente Molar/patologia , Osteoclastos/patologia , Doenças Periapicais/complicações , Doenças Periapicais/patologia , Ápice Dentário/efeitos dos fármacos , Ápice Dentário/patologia
11.
Dis Model Mech ; 9(7): 811-20, 2016 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-27482819

RESUMO

Zebrafish are a major model for chemical genetics, and most studies use embryos when investigating small molecules that cause interesting phenotypes or that can rescue disease models. Limited studies have dosed adults with small molecules by means of water-borne exposure or injection techniques. Challenges in the form of drug delivery-related trauma and anesthesia-related toxicity have excluded the adult zebrafish from long-term drug efficacy studies. Here, we introduce a novel anesthetic combination of MS-222 and isoflurane to an oral gavage technique for a non-toxic, non-invasive and long-term drug administration platform. As a proof of principle, we established drug efficacy of the FDA-approved BRAF(V600E) inhibitor, Vemurafenib, in adult zebrafish harboring BRAF(V600E) melanoma tumors. In the model, adult casper zebrafish intraperitoneally transplanted with a zebrafish melanoma cell line (ZMEL1) and exposed to daily sub-lethal dosing at 100 mg/kg of Vemurafenib for 2 weeks via oral gavage resulted in an average 65% decrease in tumor burden and a 15% mortality rate. In contrast, Vemurafenib-resistant ZMEL1 cell lines, generated in culture from low-dose drug exposure for 4 months, did not respond to the oral gavage treatment regimen. Similarly, this drug treatment regimen can be applied for treatment of primary melanoma tumors in the zebrafish. Taken together, we developed an effective long-term drug treatment system that will allow the adult zebrafish to be used to identify more effective anti-melanoma combination therapies and opens up possibilities for treating adult models of other diseases.


Assuntos
Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Avaliação Pré-Clínica de Medicamentos , Neoplasias/tratamento farmacológico , Peixe-Zebra/metabolismo , Administração Oral , Animais , Animais Geneticamente Modificados , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Indóis/farmacologia , Indóis/uso terapêutico , Melanoma/tratamento farmacológico , Melanoma/patologia , Transplante de Neoplasias , Neoplasias/patologia , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Proteínas Proto-Oncogênicas B-raf/metabolismo , Sulfonamidas/farmacologia , Sulfonamidas/uso terapêutico , Vemurafenib
12.
Adv Exp Med Biol ; 916: 103-24, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27165351

RESUMO

Chemical genetics is the use of small molecules to perturb biological pathways. This technique is a powerful tool for implicating genes and pathways in developmental programs and disease, and simultaneously provides a platform for the discovery of novel therapeutics. The zebrafish is an advantageous model for in vivo high-throughput small molecule screening due to translational appeal, high fecundity, and a unique set of developmental characteristics that support genetic manipulation, chemical treatment, and phenotype detection. Chemical genetic screens in zebrafish can identify hit compounds that target oncogenic processes-including cancer initiation and maintenance, metastasis, and angiogenesis-and may serve as cancer therapies. Notably, by combining drug discovery and animal testing, in vivo screening of small molecules in zebrafish has enabled rapid translation of hit anti-cancer compounds to the clinic, especially through the repurposing of FDA-approved drugs. Future technological advancements in automation and high-powered imaging, as well as the development and characterization of new mutant and transgenic lines, will expand the scope of chemical genetics in zebrafish.


Assuntos
Modelos Animais de Doenças , Neoplasias/tratamento farmacológico , Neoplasias/genética , Animais , Ensaios de Seleção de Medicamentos Antitumorais , Neoplasias/patologia , Peixe-Zebra
14.
J Health Care Poor Underserved ; 25(3): 1121-38, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25130229

RESUMO

This study explored the presence and characteristics of natural mentors among 197 homeless youth and the association between natural mentoring relationships and youth functioning. Few studies have explored protective factors in the lives of homeless youth and how these may buffer against poor health outcomes. Relationships with natural mentors have been shown to have protective effects on adolescent functioning among the general adolescent population, and, thus, warrant further investigation with homeless youth. Results from this study revealed that 73.6% of homeless youth have natural mentoring relationships, split between kin and non-kin relationships. Having a natural mentor was associated with higher satisfaction with social support and fewer risky sexual behaviors. Findings suggest that natural mentors may play a protective role in the lives of homeless youth and should be considered an important source of social support that may enhance youth resilience.


Assuntos
Pessoas Mal Alojadas , Mentores , Adolescente , California , Família , Feminino , Humanos , Masculino , Assunção de Riscos , Apoio Social , Adulto Jovem
15.
J Trauma Nurs ; 21(3): 133-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24828777

RESUMO

Injury prevention initiatives are an effective strategy to reduce pediatric morbidity and mortality, but resource constraints can limit hospital-based prevention programs' capacity for carrying out such initiatives. Partnerships that leverage hospital leadership roles and promote collaborative outreach may provide a less resource-intensive means to expand prevention program capacity. One hospital piloted a collaborative helmet safety initiative, partnering with a nursing school and a local school district. The purpose of this study was to evaluate the effectiveness of the resulting student nurse-administered school helmet safety program in improving use, knowledge, and attitudes toward helmets among school-age children.


Assuntos
Prevenção de Acidentes/instrumentação , Dispositivos de Proteção da Cabeça , Educação em Saúde/organização & administração , Ferimentos e Lesões/prevenção & controle , Prevenção de Acidentes/métodos , Adolescente , Ciclismo/lesões , California , Criança , Relações Comunidade-Instituição , Feminino , Humanos , Masculino , Desenvolvimento de Programas , Avaliação de Programas e Projetos de Saúde , Gestão da Segurança , Serviços de Saúde Escolar/organização & administração
16.
Issues Ment Health Nurs ; 35(3): 212-9, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24597587

RESUMO

The purpose of this cross-sectional study was to explore social connectedness and self-esteem as predictors of resilience among homeless youth with histories of maltreatment. Connectedness variables included family connectedness, school connectedness, and affiliation with prosocial peers. The sample included 150 homeless youth aged 14 to 21 (mean age = 18 years) with the majority being an ethnic minority. Participants completed surveys using audio-CASI. Results revealed that youth with higher levels of social connectedness and self-esteem reported lower levels of psychological distress. When all predictor variables were controlled in the analysis, self-esteem remained significant for predicting better mental health.


Assuntos
Maus-Tratos Infantis/psicologia , Jovens em Situação de Rua/psicologia , Transtornos Mentais/enfermagem , Transtornos Mentais/psicologia , Resiliência Psicológica , Autoimagem , Identificação Social , Apoio Social , Adolescente , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/enfermagem , Transtornos de Ansiedade/psicologia , California , Estudos Transversais , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/enfermagem , Transtorno Depressivo/psicologia , Relações Familiares , Feminino , Humanos , Acontecimentos que Mudam a Vida , Masculino , Transtornos Mentais/diagnóstico , Grupo Associado , Adulto Jovem
17.
J Child Adolesc Psychiatr Nurs ; 26(4): 246-53, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24180604

RESUMO

PROBLEM: Homeless youth experience high risks for poor mental health outcomes. The purpose of this qualitative study was to explore the characteristics of natural mentoring relationships among homeless youth and to identify possible mechanisms that can enhance social support for this population. METHODS: Semi-structured interviews were conducted with 23 homeless youth aged 14-21 who had natural mentors. The interviews focused on how youth met their natural mentors, the function of these relationships, and how natural mentoring relationships differed from other relationships in the youth's social networks. FINDINGS: Main themes that emerged from the interviews included parental absence, natural mentors as surrogate parents, and social support from mentors. CONCLUSIONS: Findings suggest that social supports provided by mentors enhance youth's adaptive functioning and may promote resilience, thus the use of natural mentors may be an important untapped asset in designing interventions to improve outcomes for homeless youth.


Assuntos
Jovens em Situação de Rua/psicologia , Relações Interpessoais , Apoio Social , Adolescente , Adulto , Feminino , Humanos , Masculino , Mentores/psicologia , Adulto Jovem
18.
Proc Natl Acad Sci U S A ; 110(24): 9776-81, 2013 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-23720309

RESUMO

Ectodomain cleavage of cell-surface proteins by A disintegrin and metalloproteinases (ADAMs) is highly regulated, and its dysregulation has been linked to many diseases. ADAM10 and ADAM17 cleave most disease-relevant substrates. Broad-spectrum metalloprotease inhibitors have failed clinically, and targeting the cleavage of a specific substrate has remained impossible. It is therefore necessary to identify signaling intermediates that determine substrate specificity of cleavage. We show here that phorbol ester or angiotensin II-induced proteolytic release of EGF family members may not require a significant increase in ADAM17 protease activity. Rather, inducers activate a signaling pathway using PKC-α and the PKC-regulated protein phosphatase 1 inhibitor 14D that is required for ADAM17 cleavage of TGF-α, heparin-binding EGF, and amphiregulin. A second pathway involving PKC-δ is required for neuregulin (NRG) cleavage, and, indeed, PKC-δ phosphorylation of serine 286 in the NRG cytosolic domain is essential for induced NRG cleavage. Thus, signaling-mediated substrate selection is clearly distinct from regulation of enzyme activity, an important mechanism that offers itself for application in disease.


Assuntos
Proteínas ADAM/metabolismo , Fator de Crescimento Epidérmico/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador alfa/metabolismo , Proteínas ADAM/genética , Proteína ADAM17 , Anfirregulina , Angiotensina II/farmacologia , Western Blotting , Linhagem Celular Tumoral , Família de Proteínas EGF , Ativação Enzimática/efeitos dos fármacos , Citometria de Fluxo , Glicoproteínas/genética , Glicoproteínas/metabolismo , Células HEK293 , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Isoenzimas/metabolismo , Células Jurkat , Ligantes , Fosforilação , Proteína Quinase C/metabolismo , Proteínas/metabolismo , Proteólise/efeitos dos fármacos , Interferência de RNA , Serina/genética , Serina/metabolismo , Especificidade por Substrato , Acetato de Tetradecanoilforbol/farmacologia , Fator de Crescimento Transformador alfa/genética
19.
Public Health Nurs ; 29(4): 313-9, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22765243

RESUMO

Runaway and homeless youth face multiple challenges to their health and experience inadequate access to health care services. This article describes a web-based personal health information system (PHIS) called Healthshack that was specifically designed to improve health care access and health outcomes for runaway and homeless youth at a community-based agency that served homeless youth and young adults up to age 24. The program was developed in partnership with homeless youth and piloted by public health nurses. Preliminary findings from the program indicate that a PHIS is acceptable to runaway and homeless youth and feasible to incorporate into the flow of a youth agency. Thus, a PHIS may be an innovative model of service delivery for other marginalized populations.


Assuntos
Serviços de Saúde Comunitária/organização & administração , Jovens em Situação de Rua , Sistemas de Informação , Internet , Sistemas Computadorizados de Registros Médicos , Adolescente , Criança , Feminino , Acessibilidade aos Serviços de Saúde , Humanos , Relações Interinstitucionais , Masculino , Aceitação pelo Paciente de Cuidados de Saúde , Serviço Social , Estados Unidos , Adulto Jovem
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