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1.
Anesth Analg ; 129(3): 701-708, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31425209

RESUMO

BACKGROUND: Ketorolac tromethamine has been used for joint infiltration by the orthopedic surgeons as a part of postoperative multimodal analgesia. The objective of this study is to investigate the pharmacokinetic properties of S (-) and R (+) enantiomers of ketorolac in adult patients undergoing total hip (THA) and knee arthroplasty (TKA). METHODS: Adult patients with normal preoperative renal function received a periarticular infiltration of 30 mg of ketorolac tromethamine along with 100 mL of 0.2% ropivacaine and 1 mg of epinephrine at the end of their THA or TKA surgery. Blood samples were taken from a venous cannula at various time points after infiltration. Pharmacokinetic modeling was performed using PMetrics 1.5.0. RESULTS: From 18 participants, 104 samples were analyzed. The peak plasma concentration for S (-) ketorolac was found to be lower than that of R (+) ketorolac, for both THA (0.19-1.22 mg/L vs 0.39-1.63 mg/L, respectively) and TKA (0.28-0.60 mg/L vs 0.48-0.88 mg/L, respectively). The clearance of the S (-) ketorolac enantiomer was higher than R (+) ketorolac (4.50 ± 2.27 vs 1.40 ± 0.694 L/h, respectively). CONCLUSIONS: Our study demonstrates that with periarticular infiltration, S (-) ketorolac was observed to have increased clearance rate and highly variable volume of distribution and lower peak plasma concentration compared to R (+) ketorolac.


Assuntos
Anti-Inflamatórios não Esteroides/farmacocinética , Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Cápsula Articular/metabolismo , Cetorolaco/farmacocinética , Dor Pós-Operatória/sangue , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios não Esteroides/administração & dosagem , Artroplastia de Quadril/tendências , Artroplastia do Joelho/tendências , Feminino , Humanos , Cápsula Articular/efeitos dos fármacos , Cetorolaco/administração & dosagem , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/tratamento farmacológico
2.
Circ Res ; 119(3): 450-62, 2016 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-27245171

RESUMO

RATIONALE: Blood flow-induced shear stress controls endothelial cell (EC) physiology during atherosclerosis via transcriptional mechanisms that are incompletely understood. The mechanosensitive transcription factor TWIST is expressed during embryogenesis, but its role in EC responses to shear stress and focal atherosclerosis is unknown. OBJECTIVE: To investigate whether TWIST regulates endothelial responses to shear stress during vascular dysfunction and atherosclerosis and compare TWIST function in vascular development and disease. METHODS AND RESULTS: The expression and function of TWIST1 was studied in EC in both developing vasculature and during the initiation of atherosclerosis. In zebrafish, twist was expressed in early embryonic vasculature where it promoted angiogenesis by inducing EC proliferation and migration. In adult porcine and murine arteries, TWIST1 was expressed preferentially at low shear stress regions as evidenced by quantitative polymerase chain reaction and en face staining. Moreover, studies of experimental murine carotid arteries and cultured EC revealed that TWIST1 was induced by low shear stress via a GATA4-dependent transcriptional mechanism. Gene silencing in cultured EC and EC-specific genetic deletion in mice demonstrated that TWIST1 promoted atherosclerosis by inducing inflammation and enhancing EC proliferation associated with vascular leakiness. CONCLUSIONS: TWIST expression promotes developmental angiogenesis by inducing EC proliferation and migration. In addition to its role in development, TWIST is expressed preferentially at low shear stress regions of adult arteries where it promotes atherosclerosis by inducing EC proliferation and inflammation. Thus, pleiotropic functions of TWIST control vascular disease and development.


Assuntos
Aterosclerose/metabolismo , Velocidade do Fluxo Sanguíneo/fisiologia , Endotélio Vascular/metabolismo , Proteínas Nucleares/biossíntese , Proteína 1 Relacionada a Twist/biossíntese , Animais , Aterosclerose/patologia , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Células Cultivadas , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Endotélio Vascular/patologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Masculino , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Suínos , Peixe-Zebra
3.
J Cell Sci ; 128(7): 1408-21, 2015 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-25681501

RESUMO

Wnt signalling plays essential roles during embryonic development and is known to be mis-regulated in human disease. There are many molecular mechanisms that ensure tight regulation of Wnt activity. One such regulator is the heparan-sulfate-specific 6-O-endosulfatase Sulf1. Sulf1 acts extracellularly to modify the structure of heparan sulfate chains to affect the bio-availability of Wnt ligands. Sulf1 could, therefore, influence the formation of Wnt signalling complexes to modulate the activation of both canonical and non-canonical pathways. In this study, we use well-established assays in Xenopus to investigate the ability of Sulf1 to modify canonical and non-canonical Wnt signalling. In addition, we model the ability of Sulf1 to influence morphogen gradients using fluorescently tagged Wnt ligands in ectodermal explants. We show that Sulf1 overexpression has ligand-specific effects on Wnt signalling: it affects membrane accumulation and extracellular levels of tagged Wnt8a and Wnt11b ligands differently, and inhibits the activity of canonical Wnt8a but enhances the activity of non-canonical Wnt11b.


Assuntos
Transdução de Sinais , Sulfatases/metabolismo , Proteínas Wnt/metabolismo , Proteína Wnt3A/metabolismo , Proteínas de Xenopus/metabolismo , Xenopus laevis/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Animais , Ligantes , Sulfatases/genética , Proteínas Wnt/genética , Proteína Wnt3A/genética , Proteínas de Xenopus/genética , Xenopus laevis/embriologia , Xenopus laevis/genética , Proteínas de Peixe-Zebra/genética
4.
Development ; 140(5): 976-86, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23344711

RESUMO

Lin28 family proteins share a unique structure, with both zinc knuckle and cold shock RNA-binding domains, and were originally identified as regulators of developmental timing in Caenorhabditis elegans. They have since been implicated as regulators of pluripotency in mammalian stem cells in culture. Using Xenopus tropicalis, we have undertaken the first analysis of the effects on the early development of a vertebrate embryo resulting from global inhibition of the Lin28 family. The Xenopus genome contains two Lin28-related genes, lin28a and lin28b. lin28a is expressed zygotically, whereas lin28b is expressed both zygotically and maternally. Both lin28a and lin28b are expressed in pluripotent cells of the Xenopus embryo and are enriched in cells that respond to mesoderm-inducing signals. The development of axial and paraxial mesoderm is severely abnormal in lin28 knockdown (morphant) embryos. In culture, the ability of pluripotent cells from the embryo to respond to the FGF and activin/nodal-like mesoderm-inducing pathways is compromised following inhibition of lin28 function. Furthermore, there are complex effects on the temporal regulation of, and the responses to, mesoderm-inducing signals in lin28 morphant embryos. We provide evidence that Xenopus lin28 proteins play a key role in choreographing the responses of pluripotent cells in the early embryo to the signals that regulate germ layer specification, and that this early function is probably independent of the recognised role of Lin28 proteins in negatively regulating let-7 miRNA biogenesis.


Assuntos
Camadas Germinativas/embriologia , Proteínas de Ligação a RNA/fisiologia , Proteínas de Xenopus/fisiologia , Xenopus/embriologia , Animais , Animais Geneticamente Modificados , Padronização Corporal/efeitos dos fármacos , Padronização Corporal/genética , Clonagem Molecular , Embrião não Mamífero , Fatores de Crescimento de Fibroblastos/metabolismo , Fatores de Crescimento de Fibroblastos/farmacologia , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Camadas Germinativas/efeitos dos fármacos , Camadas Germinativas/metabolismo , Morfolinos/farmacologia , Isoformas de Proteínas/antagonistas & inibidores , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Proteínas de Ligação a RNA/antagonistas & inibidores , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Distribuição Tecidual/efeitos dos fármacos , Xenopus/genética , Xenopus/metabolismo , Proteínas de Xenopus/antagonistas & inibidores , Proteínas de Xenopus/genética , Proteínas de Xenopus/metabolismo
5.
Dev Biol ; 391(2): 207-18, 2014 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-24768893

RESUMO

Genetic studies have established that heparan sulphate proteoglycans (HSPGs) are required for signalling by key developmental regulators, including Hedgehog, Wnt/Wg, FGF, and BMP/Dpp. Post-synthetic remodelling of heparan sulphate (HS) by Sulf1 has been shown to modulate these same signalling pathways. Sulf1 codes for an N-acetylglucosamine 6-O-endosulfatase, an enzyme that specifically removes the 6-O sulphate group from glucosamine in highly sulfated regions of HS chains. One striking aspect of Sulf1 expression in all vertebrates is its co-localisation with that of Sonic hedgehog in the floor plate of the neural tube. We show here that Sulf1 is required for normal specification of neural progenitors in the ventral neural tube, a process known to require a gradient of Shh activity. We use single-cell injection of mRNA coding for GFP-tagged Shh in early Xenopus embryos and find that Sulf1 restricts ligand diffusion. Moreover, we find that the endogenous distribution of Shh protein in Sulf1 knockdown embryos is altered, where a less steep ventral to dorsal gradient forms in the absence of Sulf1, resulting in more a diffuse distribution of Shh. These data point to an important role for Sulf1 in the ventral neural tube, and suggests a mechanism whereby Sulf1 activity shapes the Shh morphogen gradient by promoting ventral accumulation of high levels of Shh protein.


Assuntos
Padronização Corporal/genética , Proteínas Hedgehog/metabolismo , Tubo Neural/embriologia , Sulfotransferases/fisiologia , Proteínas de Xenopus/metabolismo , Proteínas de Xenopus/fisiologia , Xenopus/embriologia , Animais , Regulação da Expressão Gênica no Desenvolvimento , Proteínas Hedgehog/biossíntese , Proteínas Hedgehog/genética , Heparitina Sulfato/metabolismo , RNA Mensageiro , Transdução de Sinais/genética , Sulfotransferases/genética , Proteínas de Xenopus/biossíntese , Proteínas de Xenopus/genética
6.
Ann Med Surg (Lond) ; 86(9): 5017-5023, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39238998

RESUMO

Background: The COVID-19 pandemic has created challenges in the diagnosis and management of colorectal cancer (CRC). It was proposed in regional Northern Australia that the distance to services could further impact cancer outcomes, leading to delayed diagnosis. The authors compared the outcomes of patients prior and during the pandemic; with a focus on whether patients were presenting in the emergency setting with more advanced disease. The distance to treatment was also analysed to see if there was any impact to the management of patients with colorectal cancer. Methods: A retrospective analysis of 444 patients who underwent treatment for colorectal cancer over two time periods was examined. Time period 1 (prior to COVID-19); March 2017-July 2019 and time period 2 (during COVID-19); March 2020-July 2022. Only patients with colorectal adenocarcinoma were included if they were primarily treated at a hospital in northern Australia; those with benign pathologies or recurrent disease were also excluded. Data was collected in terms of treatment and outcomes and compared between the two groups. A separate analysis of whether locality affected outcomes and referral times was also performed. Results: In the time period prior to COVID-19, 174 patients' required invasive management, while in the second time period during COVID-19, there were 188 patients managed surgically or endoscopically. Of the patients managed prior to COVID-19 17/174 (9.8%) patients required emergency interventions, during COVID-19 this number increased to 37/188 (19.7%). This difference was deemed to be statistically significant (P =0.008). No substantial difference in cancer staging at presentation was found between the two groups. There was an increase in complication rate found during COVID-19 34.6 vs 25.5% prior to COVID-19 (P=0.046). During COVID-19, the median time between General Practitioner (primary care physician) referral and colonoscopy was actually lower than prior to covid 26.5 vs 36 days (P=0.047). When comparing local to distant patients, we found locally based patients had lower rates of neoadjuvant treatment 18.9 vs 30.4% (P=0.018) and higher rates of open surgery 39.1 vs 26.5%, P =0.012. An increase in time between colonoscopy and outpatient department review (OPD) was seen in patients not from the local area 13 vs 18 days (P =0.006). Conclusion: The authors found during the COVID-19 pandemic a greater proportion of patients were presenting with colorectal cancer that required emergency intervention. This may be due to decreased presentations to general practitioners due to lockdown causing potential delays in diagnosis. The authors did not see more advanced disease in these patients presenting emergently, between the two groups. Further assessment of local patients' vs patients from distant sites, showed difference in how patients were managed but similar outcomes. Our large catchment area with distance to treatment in Northern Australia may further impact the management of colorectal cancer in the future.

7.
Dev Biol ; 371(2): 256-68, 2012 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-22954963

RESUMO

In order to identify early transcriptional targets of MyoD prior to skeletal muscle differentiation, we have undertaken a transcriptomic analysis on gastrula stage Xenopus embryos in which MyoD has been knocked-down. Our validated list of genes transcriptionally regulated by MyoD includes Esr1 and Esr2, which are known targets of Notch signalling, and Tbx6, mesogenin, and FoxC1; these genes are all are known to be essential for normal somitogenesis but are expressed surprisingly early in the mesoderm. In addition we found that MyoD is required for the expression of myf5 in the early mesoderm, in contrast to the reverse relationship of these two regulators in amniote somites. These data highlight a role for MyoD in the early mesoderm in regulating a set of genes that are essential for both myogenesis and somitogenesis.


Assuntos
Desenvolvimento Muscular/genética , Proteína MyoD/genética , Somitos/embriologia , Transcrição Gênica , Animais , Embrião não Mamífero/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Técnicas de Silenciamento de Genes , Proteína MyoD/metabolismo , Fator Regulador Miogênico 5/genética , Fator Regulador Miogênico 5/metabolismo , Receptores Notch/genética , Receptores Notch/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Somitos/metabolismo , Transcriptoma , Proteínas de Xenopus/genética , Proteínas de Xenopus/metabolismo , Xenopus laevis
8.
BMJ Open ; 13(3): e069665, 2023 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-36863742

RESUMO

INTRODUCTION: There is an increasing concern about the misuse of prescription drugs. Misuse refers to the intentional repurposing of prescribed drugs and/or the use of illicitly sourced prescription drugs, which may be counterfeit or contaminated. Drugs with the greatest potential for misuse are prescription opioids, gabapentinoids, benzodiazepines, Z-drugs and stimulants. OBJECTIVE: The aim of this study is to provide a comprehensive analysis of the supply, patterns of use and health burden associated with prescription drugs with potential for misuse (PDPM) in Ireland between 2010 and 2020. Three inter-related studies will be carried out. The first study will describe trends in supply of PDPM using law enforcement drug seizures data and national prescription records from national community and prison settings. The second study aims to estimate trends in the detection of PDPM across multiple early warning systems using national forensic toxicology data. The third study aims to quantify the health burden associated with PDPM nationally, using epidemiological indicators of drug-poisoning deaths, non-fatal intentional drug overdose presentations to hospitals and drug treatment demand. METHODS AND ANALYSIS: A retrospective observational study design, with repeated cross-sectional analyses, using negative binomial regression models or, where appropriate, joinpoint regression. ETHICS AND DISSEMINATION: The study has received approval from the RCSI Ethics Committee (REC202202020). Results will be disseminated in peer-reviewed journals, scientific and drug policy meetings and with key stakeholders via research briefs.


Assuntos
Medicamentos sob Prescrição , Humanos , Analgésicos Opioides , Estudos Transversais , Irlanda/epidemiologia , Prescrições
9.
Int J Surg Case Rep ; 18: 12-4, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26670411

RESUMO

INTRODUCTION: Cystadenoma of apocrine origin is a tumour of the sweat gland that is benign in nature. Classification of this pathology is based upon histological characteristics plus histochemical analysis. Prevalence of cystadenoma has been suggested to be quite rare, in the region of 1 in 1000 of subcutaneous biopsies observed. PRESENTATION OF CASE: We present a case of a 40 year old man referred by his GP with a suboccipital lump, present for some years. On examination the lump was approximately 4-5cm in diameter and an unusual punctum was present. The patient proceeded to an excision of the lesion and the gross specimen showed characteristics of a multiloculated cyst, measuring some 5cm×3.5cm. Histopathology of the tumour revealed an apocrine cystadenoma; there were no features suggestive of malignancy. DISCUSSION: Previous classification of cystadenoma via histological and immunohistochemical method; has revealed only two distinct entities and the term hydrocystoma was often used in place of cystadenoma. More recent studies have suggested that a third type can be identified via immunohistochemical analysis. This third type; apocrine hydrocystoma, reveals that those previously defined as eccrine in origin may also be related to the apocrine ducts. CONCLUSION: Apocrine cystadenoma remains a benign pathology and treatment should be focussed on excision, without need for further intervention. Apocrine cystadenoma remains a relatively rare pathology, though one which should not recur if adequate treatment is given.

10.
Int J Surg Case Rep ; 19: 137-9, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26764887

RESUMO

INTRODUCTION: Dermatofibrosarcoma Protuberans is an uncommon tumour, making up less than 0.1% of all malignancies. With regards to soft tissue tumours; this pathology is thought to make up less than 2% of the sum total. Traditionally treatment has been wide local excision, with or without adjuvant radiotherapy. PRESENTATION OF CASE: We present a case of a 42 year old man referred by his GP with a lump on the right parietal region of the scalp. An USS done by his GP revealed a complex hypoechoic cystic mass, some 2cm×1cm×2cm. Excision biopsy was performed and on review of the pathology it was noted that the lesion was a Dermatofibrosarcoma Protuberans. Due to the relatively low grade of this sarcoma, it was decided to treat with wide local excision with 2-4cm margins. The expected residual scalp defect would be difficult to close with local flaps. To facilitate closure tissue expansion was undertaken for 6 weeks prior to definitive surgery. DISCUSSION: With regards to tumours of the head and neck, use of a tissue expander has been recommended to improve cosmetic outcomes following respective surgery with wide margins. Ultimately the timing of tissue expansion i.e. before/after resection of the tumour, must weight the risk of delayed resective surgery on prognosis against the benefits of this reconstructive technique. CONCLUSION: Head and neck tumours requiring careful reconstruction may benefit from tissue expansion to provide adequate volumes of matching soft tissue, as shown in this case.

11.
J Vis Exp ; (106): e53162, 2015 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-26709854

RESUMO

This protocol describes a method to visualise ligands distributed across a field of cells. The ease of expressing exogenous proteins, together with the large size of their cells in early embryos, make Xenopus laevis a useful model for visualising GFP-tagged ligands. Synthetic mRNAs are efficiently translated after injection into early stage Xenopus embryos, and injections can be targeted to a single cell. When combined with a lineage tracer such as membrane tethered RFP, the injected cell (and its descendants) that are producing the overexpressed protein can easily be followed. This protocol describes a method for the production of fluorescently tagged Wnt and Shh ligands from injected mRNA. The methods involve the micro dissection of ectodermal explants (animal caps) and the analysis of ligand diffusion in multiple samples. By using confocal imaging, information about ligand secretion and diffusion over a field of cells can be obtained. Statistical analyses of confocal images provide quantitative data on the shape of ligand gradients. These methods may be useful to researchers who want to test the effects of factors that may regulate the shape of morphogen gradients.


Assuntos
Proteínas Hedgehog/metabolismo , Microscopia Confocal/métodos , Proteínas Wnt/metabolismo , Proteínas de Xenopus/metabolismo , Xenopus laevis/metabolismo , Animais , Ectoderma/metabolismo , Feminino , Proteínas Hedgehog/biossíntese , Proteínas Hedgehog/genética , Ligantes , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais , Proteínas Wnt/biossíntese , Proteínas Wnt/genética , Proteínas de Xenopus/biossíntese , Proteínas de Xenopus/genética
12.
IET Syst Biol ; 9(6): 226-33, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26577157

RESUMO

This study describes how the application of evolutionary algorithms (EAs) can be used to study motor function in humans with Parkinson's disease (PD) and in animal models of PD. Human data is obtained using commercially available sensors via a range of non-invasive procedures that follow conventional clinical practice. EAs can then be used to classify human data for a range of uses, including diagnosis and disease monitoring. New results are presented that demonstrate how EAs can also be used to classify fruit flies with and without genetic mutations that cause Parkinson's by using measurements of the proboscis extension reflex. The case is made for a computational approach that can be applied across human and animal studies of PD and lays the way for evaluation of existing and new drug therapies in a truly objective way.


Assuntos
Algoritmos , Antiparkinsonianos/uso terapêutico , Diagnóstico por Computador/métodos , Doença de Parkinson/diagnóstico , Doença de Parkinson/tratamento farmacológico , Animais , Drosophila melanogaster , Feminino , Humanos , Masculino , Peixe-Zebra
13.
PLoS One ; 10(10): e0141611, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26506092

RESUMO

INTRODUCTION AND OBJECTIVES: The zinc-finger transcription factor Krϋppel-like factor 2 (KLF2) transduces blood flow into molecular signals responsible for a wide range of responses within the vasculature. KLF2 maintains a healthy, quiescent endothelial phenotype. Previous studies report a range of phenotypes following morpholino antisense oligonucleotide-induced klf2a knockdown in zebrafish. Targeted genome editing is an increasingly applied method for functional assessment of candidate genes. We therefore generated a stable klf2a mutant zebrafish and characterised its cardiovascular and haematopoietic development. METHODS AND RESULTS: Using Transcription Activator-Like Effector Nucleases (TALEN) we generated a klf2a mutant (klf2ash317) with a 14bp deletion leading to a premature stop codon in exon 2. Western blotting confirmed loss of wild type Klf2a protein and the presence of a truncated protein in klf2ash317 mutants. Homozygous klf2ash317 mutants exhibit no defects in vascular patterning, survive to adulthood and are fertile, without displaying previously described morphant phenotypes such as high-output cardiac failure, reduced haematopoetic stem cell (HSC) development or impaired formation of the 5th accessory aortic arch. Homozygous klf2ash317 mutation did not reduce angiogenesis in zebrafish with homozygous mutations in von Hippel Lindau (vhl), a form of angiogenesis that is dependent on blood flow. We examined expression of three klf family members in wildtype and klf2ash317 zebrafish. We detected vascular expression of klf2b (but not klf4a or biklf/klf4b/klf17) in wildtypes but found no differences in expression that might account for the lack of phenotype in klf2ash317 mutants. klf2b morpholino knockdown did not affect heart rate or impair formation of the 5th accessory aortic arch in either wildtypes or klf2ash317 mutants. CONCLUSIONS: The klf2ash317 mutation produces a truncated Klf2a protein but, unlike morpholino induced klf2a knockdown, does not affect cardiovascular development.


Assuntos
Sistema Cardiovascular/crescimento & desenvolvimento , Sistema Hematopoético/crescimento & desenvolvimento , Fatores de Transcrição Kruppel-Like/genética , Morfogênese/genética , Proteínas de Peixe-Zebra/genética , Animais , Regulação da Expressão Gênica no Desenvolvimento , Genótipo , Humanos , Fatores de Transcrição Kruppel-Like/antagonistas & inibidores , Fatores de Transcrição Kruppel-Like/biossíntese , Morfolinos/genética , Mutação , Transdução de Sinais , Peixe-Zebra/genética , Peixe-Zebra/crescimento & desenvolvimento , Proteínas de Peixe-Zebra/antagonistas & inibidores , Proteínas de Peixe-Zebra/biossíntese
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