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1.
Annu Rev Cell Dev Biol ; 36: 385-410, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-32628862

RESUMO

Development encapsulates the morphogenesis of an organism from a single fertilized cell to a functional adult. A critical part of development is the specification of organ forms. Beyond the molecular control of morphogenesis, shape in essence entails structural constraints and thus mechanics. Revisiting recent results in biophysics and development, and comparing animal and plant model systems, we derive key overarching principles behind the formation of organs across kingdoms. In particular, we highlight how growing organs are active rather than passive systems and how such behavior plays a role in shaping the organ. We discuss the importance of considering different scales in understanding how organs form. Such an integrative view of organ development generates new questions while calling for more cross-fertilization between scientific fields and model system communities.


Assuntos
Morfogênese , Especificidade de Órgãos , Animais , Anisotropia , Fenômenos Biomecânicos , Humanos , Mecanotransdução Celular , Modelos Biológicos
2.
Proc Natl Acad Sci U S A ; 116(51): 25430-25439, 2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31772022

RESUMO

Organ formation is an inherently biophysical process, requiring large-scale tissue deformations. Yet, understanding how complex organ shape emerges during development remains a major challenge. During zebrafish embryogenesis, large muscle segments, called myotomes, acquire a characteristic chevron morphology, which is believed to aid swimming. Myotome shape can be altered by perturbing muscle cell differentiation or the interaction between myotomes and surrounding tissues during morphogenesis. To disentangle the mechanisms contributing to shape formation of the myotome, we combine single-cell resolution live imaging with quantitative image analysis and theoretical modeling. We find that, soon after segmentation from the presomitic mesoderm, the future myotome spreads across the underlying tissues. The mechanical coupling between the future myotome and the surrounding tissues appears to spatially vary, effectively resulting in spatially heterogeneous friction. Using a vertex model combined with experimental validation, we show that the interplay of tissue spreading and friction is sufficient to drive the initial phase of chevron shape formation. However, local anisotropic stresses, generated during muscle cell differentiation, are necessary to reach the acute angle of the chevron in wild-type embryos. Finally, tissue plasticity is required for formation and maintenance of the chevron shape, which is mediated by orientated cellular rearrangements. Our work sheds light on how a spatiotemporal sequence of local cellular events can have a nonlocal and irreversible mechanical impact at the tissue scale, leading to robust organ shaping.


Assuntos
Fricção/fisiologia , Músculos , Somitos , Animais , Fenômenos Biomecânicos/fisiologia , Células Cultivadas , Embrião não Mamífero/citologia , Embrião não Mamífero/fisiologia , Desenvolvimento Embrionário/fisiologia , Modelos Biológicos , Músculos/citologia , Músculos/embriologia , Análise de Célula Única , Somitos/citologia , Somitos/embriologia , Peixe-Zebra
3.
Hum Mol Genet ; 27(1): 107-119, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29126155

RESUMO

Genital malformations are among the most common human birth defects, and both genetic and environmental factors can contribute to these malformations. Development of the external genitalia in mammals relies on complex signaling networks, and disruption of these signaling pathways can lead to genital defects. Islet-1 (ISL1), a member of the LIM/Homeobox family of transcription factors, has been identified as a major susceptibility gene for classic bladder exstrophy in humans, a common form of the bladder exstrophy-epispadias complex (BEEC), and is implicated in a role in urinary tract development. We report that deletion of Isl1 from the genital mesenchyme in mice led to hypoplasia of the genital tubercle and prepuce, with an ectopic urethral opening and epispadias-like phenotype. These mice also developed hydroureter and hydronephrosis. Identification of ISL1 transcriptional targets via ChIP-Seq and expression analyses revealed that Isl1 regulates several important signaling pathways during embryonic genital development, including the BMP, WNT, and FGF cascades. An essential function of Isl1 during development of the external genitalia is to induce Bmp4-mediated apoptosis in the genital mesenchyme. Together, these studies demonstrate that Isl1 plays a critical role during development of the external genitalia and forms the basis for a greater understanding of the molecular mechanisms underlying the pathogenesis of BEEC and urinary tract defects in humans.


Assuntos
Proteína Morfogenética Óssea 4/genética , Fator 10 de Crescimento de Fibroblastos/genética , Genitália/anormalidades , Genitália/embriologia , Proteínas com Homeodomínio LIM/genética , Fatores de Transcrição/genética , Proteína Wnt-5a/genética , Animais , Extrofia Vesical/genética , Extrofia Vesical/metabolismo , Proteína Morfogenética Óssea 4/biossíntese , Proteína Morfogenética Óssea 4/metabolismo , Desenvolvimento Embrionário , Feminino , Fator 10 de Crescimento de Fibroblastos/biossíntese , Fator 10 de Crescimento de Fibroblastos/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Genitália/metabolismo , Proteínas com Homeodomínio LIM/biossíntese , Proteínas com Homeodomínio LIM/metabolismo , Masculino , Mesoderma/embriologia , Mesoderma/metabolismo , Camundongos , Camundongos Knockout , Organogênese/genética , Transdução de Sinais , Fatores de Transcrição/biossíntese , Fatores de Transcrição/metabolismo , Anormalidades Urogenitais/genética , Anormalidades Urogenitais/metabolismo , Proteína Wnt-5a/biossíntese , Proteína Wnt-5a/metabolismo
4.
Clin Otolaryngol ; 42(6): 1338-1342, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28561944

RESUMO

OBJECTIVE: Bibliometrics uses analysis of content and citations of journal articles to quantify trends in published data. We aim to use bibliometric analysis to identify the global contribution by country to the ENT surgical literature over a 5-year period. DATA SOURCE: The top 20 countries for number of articles published in surgery and the 11 English-language otolaryngology surgical journals with the highest impact factors (IF) were included. Numbers of scientific articles per year (2009-2013) per country for each journal were identified through PubMed. As a marker of quality, a mean IF for each country was calculated, using number of articles and journal IF. These data were compared against population, GDP and dollars spent on research. RESULTS: In total, 10 574 articles were included. The USA was the largest contributor, with 4462 articles published over 5 years. The second largest was the UK (1215 articles). Spain's mean IF was 2.136, followed by Taiwan (2.110). The Netherlands (19.7) and the UK (18.9) had the highest number of publications per million population. When considering overall research spending per country, Greece had the most cost-effective publication output. The least cost-effective country was Japan. India, Greece and Japan had the greatest increase in publication quality. CONCLUSIONS: Bibliometric analysis can be used to identify not only major centres of English-language ENT surgical research, such as the USA and UK but centres that are producing high-quality data, such as Spain, and cost-effective research, such as the UK. It can also highlight areas of increasing success in ENT research.


Assuntos
Bibliometria , Pesquisa Biomédica , Internacionalidade , Otolaringologia , Humanos
5.
Dev Biol ; 386(1): 1-11, 2014 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-24361260

RESUMO

Development of the mammalian external genitalia is controlled by a network of signaling molecules and transcription factors. Because FGF signaling plays a central role in this complicated morphogenetic process, we investigated the role of Sprouty genes, which are important intracellular modulators of FGF signaling, during embryonic development of the external genitalia in mice. We found that Sprouty genes are expressed by the urethral epithelium during embryogenesis, and that they have a critical function during urethral canalization and fusion. Development of the genital tubercle (GT), the anlage of the prepuce and glans penis in males and glans clitoris in females, was severely affected in male embryos carrying null alleles of both Spry1 and Spry2. In Spry1(-/-);Spry2(-/-) embryos, the internal tubular urethra was absent, and urothelial morphology and organization was abnormal. These effects were due, in part, to elevated levels of epithelial cell proliferation in Spry1(-/-);Spry2(-/-) embryos. Despite changes in overall organization, terminal differentiation of the urothelium was not significantly affected. Characterization of the molecular pathways that regulate normal GT development confirmed that deletion of Sprouty genes leads to elevated FGF signaling, whereas levels of signaling in other cascades were largely preserved. Together, these results show that levels of FGF signaling must be tightly regulated during embryonic development of the external genitalia in mice, and that this regulation is mediated in part through the activity of Sprouty gene products.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Regulação da Expressão Gênica no Desenvolvimento , Genitália/embriologia , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Proteínas de Membrana/fisiologia , Fosfoproteínas/fisiologia , Uretra/embriologia , Animais , Proliferação de Células , Feminino , Fatores de Crescimento de Fibroblastos/metabolismo , Deleção de Genes , Imuno-Histoquímica , Hibridização In Situ , Sistema de Sinalização das MAP Quinases , Masculino , Camundongos , Camundongos Transgênicos , Mutação , Proteínas Serina-Treonina Quinases , Transdução de Sinais , Fatores de Tempo , Urotélio/embriologia , Urotélio/metabolismo
6.
Intern Med J ; 44(10): 1018-26, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25302720

RESUMO

These consensus guidelines provide recommendations for the safe handling of monoclonal antibodies. Definitive recommendations are given for the minimum safe handling requirements to protect healthcare personnel. The seven recommendations cover: (i) appropriate determinants for evaluating occupational exposure risk; (ii) occupational risk level compared with other hazardous and non-hazardous drugs; (iii) stratification of risk based on healthcare personnel factors; (iv) waste products; (v) interventions and safeguards; (vi) operational and clinical factors and (vii) handling recommendations. The seventh recommendation includes a risk assessment model and flow chart for institutions to consider and evaluate clinical and operational factors unique to individual healthcare services. These guidelines specifically evaluated monoclonal antibodies used in the Australian cancer clinical practice setting; however, the principles may be applicable to monoclonal antibodies used in non-cancer settings. The guidelines are only applicable to parenterally administered agents.


Assuntos
Anticorpos Monoclonais/efeitos adversos , Fidelidade a Diretrizes , Pessoal de Saúde , Exposição Ocupacional/prevenção & controle , Saúde Ocupacional/normas , Preparações Farmacêuticas , Gestão da Segurança/normas , Austrália/epidemiologia , Consenso , Feminino , Humanos , Masculino , Medição de Risco
7.
Nat Genet ; 20(4): 353-7, 1998 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9843206

RESUMO

Ahch (also known as Dax1) encodes a transcription factor that has been implicated in sex determination and gonadal differentiation. Mutations in human AHC cause X-linked, adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism (HH). Duplication of the Xp21 dosage-sensitive sex reversal (DSS) region, which contains the Ahch locus, and transgenic overexpression of Ahch cause male-to-female sex reversal. Using Cre-mediated disruption of Ahch, we have generated a mouse model of AHC-HH that allows the function of Ahch to be examined in both males and females. Although Ahch has been postulated to function as an ovarian determination gene, the loss of Ahch function in females does not affect ovarian development or fertility. Ahch is instead essential for the maintenance of spermatogenesis. Lack of Ahch causes progressive degeneration of the testicular germinal epithelium independent of abnormalities in gonadotropin and testosterone production and results in male sterility. Ahch is thus not an ovarian determining gene, but rather has a critical role in spermatogenesis.


Assuntos
Proteínas de Ligação a DNA/fisiologia , Gônadas/embriologia , Oócitos/citologia , Espermatozoides/citologia , Glândulas Suprarrenais/anatomia & histologia , Animais , Sequência de Bases , Receptor Nuclear Órfão DAX-1 , Primers do DNA , Feminino , Humanos , Masculino , Camundongos , Folículo Ovariano/anatomia & histologia , Folículo Ovariano/citologia , Testículo/anatomia & histologia , Testículo/citologia , Dedos de Zinco
8.
Nat Genet ; 29(4): 447-52, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11694879

RESUMO

The protein neural retina leucine zipper (Nrl) is a basic motif-leucine zipper transcription factor that is preferentially expressed in rod photoreceptors. It acts synergistically with Crx to regulate rhodopsin transcription. Missense mutations in human NRL have been associated with autosomal dominant retinitis pigmentosa. Here we report that deletion of Nrl in mice results in the complete loss of rod function and super-normal cone function, mediated by S cones. The photoreceptors in the Nrl-/- retina have cone-like nuclear morphology and short, sparse outer segments with abnormal disks. Analysis of retinal gene expression confirms the apparent functional transformation of rods into S cones in the Nrl-/- retina. On the basis of these findings, we postulate that Nrl acts as a 'molecular switch' during rod-cell development by directly modulating rod-specific genes while simultaneously inhibiting the S-cone pathway through the activation of Nr2e3.


Assuntos
Proteínas de Ligação a DNA/fisiologia , Proteínas do Olho/fisiologia , Células Fotorreceptoras Retinianas Bastonetes/crescimento & desenvolvimento , Fatores de Transcrição/fisiologia , Animais , Sequência de Bases , Fatores de Transcrição de Zíper de Leucina Básica , Primers do DNA , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas do Olho/genética , Proteínas do Olho/metabolismo , Imuno-Histoquímica , Zíper de Leucina , Camundongos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
10.
J Prev Alzheimers Dis ; 10(3): 543-550, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37357296

RESUMO

BACKGROUND: In the absence of preventative pharmacological interventions for Alzheimer's Disease dementia, there is a growing interest in modifiable risk factors associated with AD. Such risk factors are thought to contribute up to 40% of the risk of dementia. The Lifestyle for Brain Health (LIBRA) index, a dementia risk score which focuses exclusively on modifiable factors, has been found to be associated with increased risk of dementia and cognitive decline. It is currently unclear how the LIBRA index relates to cerebrospinal fluid (CSF) biomarkers of Alzheimer's Disease. OBJECTIVES: To examine the association between LIBRA index scores and trajectories of phospho-tau 181 and total tau in the European Prevention of Alzheimer's Dementia Longitudinal Cohort Study (EPAD LCS), and to examine whether these trajectories differ between participants with high and low CSF amyloid-beta 1-42 (Aß42). DESIGN: Analysis of CSF biomarker and LIBRA index scores from the European Prevention of Alzheimer's Dementia Longitudinal Cohort Study. SETTING: The European Prevention of Alzheimer's Dementia Longitudinal Cohort Study is a multi-centre, pan-European study. MEASUREMENTS: Cerebrospinal fluid samples were taken by lumbar puncture and analysed using electrochemiluminescence. LIBRA index scores were calculated from self-reported variables, questionnaires, and physiological measurements. RESULT: In the total sample (n = 1715; mean age = 66.0, 56.4% female), there were no significant associations between LIBRA scores (mean = 0.73 points) and rate of change in cerebrospinal fluid biomarkers. In participants with high Aß, reflecting less deposition in the brain, (n = 1134), LIBRA scores were significantly associated with the rate of change in total tau, where higher LIBRA scores (denoting higher dementia risk) were associated with increases in t-tau. There were no significant associations between LIBRA scores and change in cerebrospinal biomarkers in participants with low Aß. CONCLUSION: We found an association between modifiable risk factors and total tau accumulation in participants without dementia and without Aß accumulation. This suggests that increasing levels of total tau may be driven by factors other than Aß accumulation and highlights the need for developing and examining tau-targeting drugs in Alzheimer's Disease development.


Assuntos
Doença de Alzheimer , Humanos , Feminino , Masculino , Doença de Alzheimer/psicologia , Estudos de Coortes , Estudos Longitudinais , Proteínas tau/líquido cefalorraquidiano , Progressão da Doença , Biomarcadores/líquido cefalorraquidiano , Encéfalo , Estilo de Vida
12.
J Laryngol Otol ; 136(12): 1140-1147, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34420530

RESUMO

OBJECTIVE: Nasal chondromesenchymal hamartoma is a rare pathology that can present with a myriad of symptoms to ENT, maxillofacial and ophthalmology departments. This study reviewed the literature on nasal chondromesenchymal hamartoma as well as adding three new cases to the reported literature. METHOD: This study was an up-to-date review of the world literature with the addition of three new cases to provide the most comprehensive review to date. RESULTS: A total of 56 patients with nasal chondromesenchymal hamartoma were identified, ranging from children to adults. Nasal symptoms and ocular symptoms were most common, and surgical resection was the most frequent treatment modality. CONCLUSION: This study advocates for increased awareness of the condition associations for nasal chondromesenchymal hamartoma, multi-specialty treatment and the role for the ENT surgeon in treatment of the condition.


Assuntos
Hamartoma , Medicina , Cirurgiões , Humanos , Criança , Adulto , Hamartoma/diagnóstico , Hamartoma/cirurgia , Face , Diagnóstico Diferencial
13.
Clin Radiol ; 66(6): 551-8, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21402376

RESUMO

Basilar artery occlusion is a potentially fatal condition and imaging findings can be subtle. Prompt diagnosis is vital, as recognition may lead to therapeutic recanalization that may improve functional outcome and survival. Furthermore, cross-sectional imaging signs may help predict eventual outcome and, therefore, guide which patients should be subjected to aggressive treatment. Computed tomography (CT) signs include a hyperdense basilar artery that has a high specificity, accuracy, positive and negative predictive value. Evidence regarding the prognostic significance of the hyperdense basilar artery sign is conflicting. Early magnetic resonance imaging (MRI) features include loss of flow void, seen as increased signal intensity within the basilar artery on T2-weigted images and identification of acute thrombus, seen as intermediate signal on T1-weighted images. MRI sequences are more sensitive for early detection of acute ischaemia or infarction, ideally with diffusion-weighted imaging (DWI). Both CT and MR angiography are sensitive for detection of acute thrombus, seen as a filling defect or occlusion. These are the non-invasive imaging techniques of choice to confirm diagnosis, with perhaps the speed and accessibility of CT angiography resulting in this technique being valuable in the acute setting. Several new scoring systems based on arterial segmentation rather than global volume assessment using CT angiography source images and DWI have shown early promise in the prediction of eventual clinical outcome in order to isolate those patients who may benefit from therapeutic recanalization.


Assuntos
Artéria Basilar , Angiografia Cerebral/métodos , Hemorragia Cerebral/diagnóstico , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada por Raios X/métodos , Doença Aguda , Idoso , Estudos Transversais , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
14.
Sci Rep ; 11(1): 14091, 2021 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-34238963

RESUMO

Development of the Drosophila embryonic mesoderm is controlled through both internal and external inputs to the mesoderm. One such factor is Heartless (Htl), a Fibroblast Growth Factor Receptor (FGFR) expressed in the mesoderm. Although Htl has been extensively studied, the dynamics of its action are poorly understood after the initial phases of mesoderm formation and spreading. To begin to address this challenge, we have developed an optogenetic version of the FGFR Heartless in Drosophila (Opto-htl). Opto-htl enables us to activate the FGFR pathway in selective spatial (~ 35 µm section from one of the lateral sides of the embryo) and temporal domains (ranging from 40 min to 14 h) during embryogenesis. Importantly, the effects can be tuned by the intensity of light-activation, making this approach significantly more flexible than other genetic approaches. We performed controlled perturbations to the FGFR pathway to define the contribution of Htl signalling to the formation of the developing embryonic heart and somatic muscles. We find a direct correlation between Htl signalling dosage and number of Tinman-positive heart cells specified. Opto-htl activation favours the specification of Tinman positive cardioblasts and eliminates Eve-positive DA1 muscles. This effect is seen to increase progressively with increasing light intensity. Therefore, fine tuning of phenotypic responses to varied Htl signalling dosage can be achieved more conveniently than with other genetic approaches. Overall, Opto-htl is a powerful new tool for dissecting the role of FGFR signalling during development.


Assuntos
Proteínas de Drosophila/metabolismo , Drosophila melanogaster/embriologia , Drosophila melanogaster/metabolismo , Embrião de Mamíferos/metabolismo , Mesoderma/metabolismo , Proteínas Tirosina Quinases/metabolismo , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Transdução de Sinais , Animais , Desenvolvimento Embrionário , Luz , Músculos/metabolismo , Mutação/genética , Fenótipo , Fatores de Tempo
15.
J Exp Med ; 177(4): 999-1008, 1993 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-8459227

RESUMO

To determine the fate of anti-DNA antibody-bearing B cells in normal mice, we generated transgenic mice bearing the heavy (H) and light (L) chain genes of a well-characterized anti-double-stranded DNA antibody. This antibody was originally isolated from a diseased MRL/lpr mouse and has characteristics common to spontaneously arising anti-DNA antibodies. Results show that the H/L transgene (tg) immunoglobulin receptor is not expressed by animals bearing both tgs, although single tg animals (H or L) express their transgenes. Young H/L tg animals express few B cells, whereas adult H/L tg animals maintain almost normal B cell numbers. Analysis of the immunoglobulin receptors used by adult B cells shows that all contain the tg H chain in association with endogenous L chains. These B cells transcribe the L tg as well as the rearranged endogenous L chain gene, and loss of endogenous L chain gene transcription results in resurrection of the 3H9 H/L tg product. Examination of the endogenous L chains used by these cells shows that they represent a highly restricted subset of V genes. Taken together, these data suggest that autoreactive transgenic B cells can rearrange endogenous L chain genes to alter surface receptors. Those L chains that compete successfully with the L tg for H chain binding, and that create a nonautoreactive receptor, allow the B cell to escape deletion. We suggest that this receptor editing is a mechanism used by immature autoreactive B cells to escape tolerance.


Assuntos
Autoanticorpos/imunologia , Linfócitos B/imunologia , Tolerância Imunológica , Receptores de Antígenos de Linfócitos B/imunologia , Animais , Autoanticorpos/genética , Sequência de Bases , Southern Blotting , Linhagem Celular , DNA/imunologia , Citometria de Fluxo , Hibridomas , Cadeias Pesadas de Imunoglobulinas/genética , Cadeias Pesadas de Imunoglobulinas/imunologia , Cadeias Pesadas de Imunoglobulinas/metabolismo , Cadeias Leves de Imunoglobulina/genética , Cadeias Leves de Imunoglobulina/imunologia , Cadeias Leves de Imunoglobulina/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Dados de Sequência Molecular , Receptores de Antígenos de Linfócitos B/metabolismo , Mapeamento por Restrição
16.
PLoS Negl Trop Dis ; 14(8): e0008669, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32866146

RESUMO

Exposure of adult mosquitoes to pyriproxyfen (PPF), an analog of insect juvenile hormone (JH), has shown promise to effectively sterilize female mosquitoes. However, the underlying mechanisms of the PPF-induced decrease in mosquito fecundity are largely unknown. We performed a comprehensive study to dissect the mode of PPF action in Aedes aegypti mosquitoes. Exposure to PPF prompted the overgrowth of primary follicles in sugar-fed Ae. aegypti females but blocked the development of primary follicles at Christopher's Stage III after blood feeding. Secondary follicles were precociously activated in PPF-treated mosquitoes. Moreover, PPF substantially altered the expression of many genes that are essential for mosquito physiology and oocyte development in the fat body and ovary. In particular, many metabolic genes were differentially expressed in response to PPF treatment, thereby affecting the mobilization and utilization of energy reserves. Furthermore, PPF treatment on the previtellogenic female adults considerably modified mosquito responses to JH and 20-hydroxyecdysone (20E), two major hormones that govern mosquito reproduction. Krüppel homolog 1, a JH-inducible transcriptional regulator, showed consistently elevated expression after PPF exposure. Conversely, PPF upregulated the expression of several key players of the 20E regulatory cascades, including HR3 and E75A, in the previtellogenic stage. After blood-feeding, the expression of these 20E response genes was significantly weaker in PPF-treated mosquitoes than the solvent-treated control groups. RNAi-mediated knockdown of the Methoprene-tolerant (Met) protein, the JH receptor, partially rescued the impaired follicular development after PPF exposure and substantially increased the hatching of the eggs produced by PPF-treated female mosquitoes. Thus, the results suggested that PPF relied on Met to exert its sterilizing effects on female mosquitoes. In summary, this study finds that PPF exposure disturbs normal hormonal responses and metabolism in Ae. aegypti, shedding light on the molecular targets and the downstream signaling pathways activated by PPF.


Assuntos
Aedes/efeitos dos fármacos , Culicidae/efeitos dos fármacos , Inseticidas/farmacologia , Metoprene/metabolismo , Esterilização , Animais , Ecdisterona/farmacologia , Corpo Adiposo/crescimento & desenvolvimento , Feminino , Glicogênio/metabolismo , Proteínas de Insetos/genética , Hormônios Juvenis/farmacologia , Ovário/crescimento & desenvolvimento , Piridinas , Interferência de RNA , Triglicerídeos/metabolismo
17.
Clin Psychol Rev ; 82: 101929, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33126038

RESUMO

BACKGROUND: Acute inpatient psychiatric wards are important yet challenging environments in which to implement psychological interventions for people with schizophrenia-spectrum disorders. No meta-analysis to date has evaluated whether psychological interventions are effective in this context. METHODS: We systematically searched Embase, Medline and PsycInfo databases for randomised controlled trials (RCTs) of psychological interventions implemented in acute inpatient psychiatric settings with individuals with schizophrenia-spectrum disorders. We conducted random effects meta-analyses of between-groups outcomes at post-intervention and relapse/re-hospitalisation rates by follow-up. RESULTS: Twenty-nine trials were suitable for meta-analysis. Psychological interventions improved post-intervention positive symptoms, social functioning and treatment compliance and reduced the risk of relapse/ re-hospitalisation, relative to control conditions. Analyses of specific intervention effects found positive effects of psychoeducation on several key outcomes (power > 80%) and preliminary evidence for positive effects of acceptance and commitment therapy (ACT), cognitive behaviour therapy (CBT) and metacognitive training (MCT) on some outcomes (power < 80%). CONCLUSION: Psychological interventions can be helpful for acute inpatients with schizophrenia-spectrum disorders. However, risk of bias was often high or unclear, and some analyses were underpowered. Further research should use more rigorous RCT designs and publish meta-analysable data on positive symptoms, general psychopathology, relapse/ re-hospitalisation, social functioning and treatment compliance.


Assuntos
Terapia de Aceitação e Compromisso , Terapia Cognitivo-Comportamental , Esquizofrenia , Humanos , Pacientes Internados , Intervenção Psicossocial , Esquizofrenia/terapia
18.
Science ; 280(5368): 1444-7, 1998 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-9603735

RESUMO

The shaker-2 mouse mutation, the homolog of human DFNB3, causes deafness and circling behavior. A bacterial artificial chromosome (BAC) transgene from the shaker-2 critical region corrected the vestibular defects, deafness, and inner ear morphology of shaker-2 mice. An unconventional myosin gene, Myo15, was discovered by DNA sequencing of this BAC. Shaker-2 mice were found to have an amino acid substitution at a highly conserved position within the motor domain of this myosin. Auditory hair cells of shaker-2 mice have very short stereocilia and a long actin-containing protrusion extending from their basal end. This histopathology suggests that Myo15 is necessary for actin organization in the hair cells of the cochlea.


Assuntos
Surdez/genética , Miosinas/genética , Sequência de Aminoácidos , Animais , Sítios de Ligação , Encéfalo/metabolismo , Cromossomos Bacterianos , Surdez/patologia , Surdez/terapia , Orelha Interna/metabolismo , Feminino , Teste de Complementação Genética , Células Ciliadas Auditivas/ultraestrutura , Humanos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Camundongos Transgênicos , Miosinas/química , Miosinas/metabolismo , Fenótipo , Mutação Puntual , Transgenes
19.
Anaesthesia ; 64(12): 1312-6, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19849683

RESUMO

In adults, first responders to a cardiopulmonary arrest provide better ventilation using a laryngeal mask airway than a facemask. It is unclear if the same is true in children. We investigated this by comparing the ability of 36 paediatric ward nurses to ventilate the lungs of 99 anaesthetised children (a model for cardiopulmonary arrest) using a laryngeal mask airway and using a facemask with an oropharyngeal airway. Anteroposterior chest wall displacement was measured using an ultrasonic detector. Nurses achieved successful ventilation in 74 (75%) of cases with the laryngeal mask airway and 76 (77%) with facemask and oropharyngeal airway (p = 0.89). Median (IQR [range]) time to first breath was longer for the laryngeal mask airway (48 (39-65 [8-149])) s than the facemask/airway (35 (25-53 [14-120]) s; p < 0.0001). In 10 cases (10%) the lungs were ventilated using the laryngeal mask airway but not using the facemask/oropharyngeal airway. We conclude that ventilation is achieved rapidly using a facemask and oropharyngeal airway, and that the laryngeal mask airway may represent a useful second line option for first responders.


Assuntos
Máscaras , Respiração Artificial/instrumentação , Anestesia Geral , Criança , Pré-Escolar , Competência Clínica , Estudos Cross-Over , Feminino , Parada Cardíaca/terapia , Humanos , Lactente , Máscaras Laríngeas , Masculino , Modelos Biológicos , Orofaringe , Respiração Artificial/métodos , Respiração Artificial/enfermagem
20.
Emerg Med J ; 26(9): 662-3, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19700584

RESUMO

Dislocation of the shoulder joint is a common presentation in the emergency department, the reduction of which is usually performed under sedation. At present post-reduction x rays are taken after the patient has recovered from this sedation. If reduction is unsuccessful, repeated attempts under further sedation may be required. In this small case series, bedside ultrasound was found to be accurate in determining whether reduction had been successful.


Assuntos
Sistemas Automatizados de Assistência Junto ao Leito , Luxação do Ombro/diagnóstico por imagem , Articulação do Ombro/diagnóstico por imagem , Humanos , Luxação do Ombro/terapia , Ultrassonografia
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