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1.
Res Social Adm Pharm ; 20(9): 860-869, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38918145

RESUMO

BACKGROUND: Asthma is a common long-term condition that affects people of all ages. Evidence suggests that a significant proportion of asthma patients in the Gulf Cooperation Council (GCC) do not receive appropriate diagnosis, monitoring and/or treatment. When inadequately treated, asthma can negatively affect quality of life and may lead to hospitalisation and death. Although pharmacists play a role in asthma care globally, there appears to be no defined role for pharmacists in providing care to patients with asthma in the GCC countries. AIM: This scoping review aims to review and summarise studies conducted in the GCC countries involving pharmacists in the management of adults with asthma or evaluating pharmacists' asthma care knowledge and/or skills. METHOD: A systematic scoping review was undertaken. Seven databases were searched using relevant search terms for articles published up to May 2023. Studies that evaluated pharmacists roles, knowledge and skills in providing asthma care to adults in the United Arab Emirates (UAE), Qatar, Kuwait, Oman, Saudi Arabia, and Bahrain were considered eligible for inclusion. Extracted data were collated using tables and used to produce narrative descriptive summaries. RESULTS: Out of the 1588 search results, only seven studies met the inclusion criteria. Of those, only one developed and tested a pharmacist-led inhaler technique educational intervention in the UAE within community pharmacy setting for asthma patients. The remaining six studies assessed community pharmacists knowledge in providing asthma management and patient education in UAE, Saudi Arabia and Qatar. The quality of the included studies varied with four relying on simulated patients to assess pharmacists knowledge. The study that tested the intervention suggested improvement in inhaler technique and asthma symptoms control after receiving the intervention. The findings suggest a need to improve pharmacists knowledge of inhaler technique demonstration (mainly Metered Dose Inhalers), asthma management advice and assessment of asthma control and medication use. CONCLUSION: This review highlights a lack of research on pharmacist-led asthma interventions and identifies training needs to enable pharmacists to be involved in asthma care in the GCC countries. Future research could develop approaches involving pharmacists to improve asthma care and outcomes in the region.


Assuntos
Asma , Farmacêuticos , Papel Profissional , Humanos , Asma/tratamento farmacológico , Farmacêuticos/organização & administração , Adulto , Oriente Médio , Conhecimentos, Atitudes e Prática em Saúde , Antiasmáticos/uso terapêutico , Antiasmáticos/administração & dosagem
2.
J Neurosci Methods ; 408: 110180, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38795977

RESUMO

BACKGROUND: Accurate identification of abnormal electroencephalographic (EEG) activity is pivotal for diagnosing and treating epilepsy. Recent studies indicate that decomposing brain activity into periodic (oscillatory) and aperiodic (trend across all frequencies) components can illuminate the drivers of spectral activity changes. NEW METHODS: We analysed intracranial EEG (iEEG) data from 234 subjects, creating a normative map. This map was compared to a cohort of 63 patients with refractory focal epilepsy under consideration for neurosurgery. The normative map was computed using three approaches: (i) relative complete band power, (ii) relative band power with the aperiodic component removed, and (iii) the aperiodic exponent. Abnormalities were calculated for each approach in the patient cohort. We evaluated the spatial profiles, assessed their ability to localize abnormalities, and replicated the findings using magnetoencephalography (MEG). RESULTS: Normative maps of relative complete band power and relative periodic band power exhibited similar spatial profiles, while the aperiodic normative map revealed higher exponent values in the temporal lobe. Abnormalities estimated through complete band power effectively distinguished between good and bad outcome patients. Combining periodic and aperiodic abnormalities enhanced performance, like the complete band power approach. COMPARISON WITH EXISTING METHODS AND CONCLUSIONS: Sparing cerebral tissue with abnormalities in both periodic and aperiodic activity may result in poor surgical outcomes. Both periodic and aperiodic components do not carry sufficient information in isolation. The relative complete band power solution proved to be the most reliable method for this purpose. Future studies could investigate how cerebral location or pathology influences periodic or aperiodic abnormalities.


Assuntos
Encéfalo , Eletrocorticografia , Magnetoencefalografia , Humanos , Magnetoencefalografia/métodos , Masculino , Feminino , Adulto , Eletrocorticografia/métodos , Adulto Jovem , Encéfalo/fisiopatologia , Mapeamento Encefálico/métodos , Pessoa de Meia-Idade , Adolescente , Processamento de Sinais Assistido por Computador , Epilepsia Resistente a Medicamentos/fisiopatologia , Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsias Parciais/fisiopatologia , Epilepsias Parciais/diagnóstico , Epilepsias Parciais/cirurgia , Epilepsia/fisiopatologia , Epilepsia/diagnóstico , Estudos de Coortes , Eletroencefalografia/métodos , Ondas Encefálicas/fisiologia
3.
ArXiv ; 2023 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-37090233

RESUMO

Intracranial EEG (iEEG) is the gold standard technique for epileptogenic zone (EZ) localisation, but requires a preconceived hypothesis of the location of the epileptogenic tissue. This placement is guided by qualitative interpretations of seizure semiology, MRI, EEG and other imaging modalities, such as magnetoencephalography (MEG). Quantitative abnormality mapping using MEG has recently been shown to have potential clinical value. We hypothesised that if quantifiable MEG abnormalities were sampled by iEEG, then patients' post-resection seizure outcome may be better. Thirty-two individuals with refractory neocortical epilepsy underwent MEG and subsequent iEEG recordings as part of pre-surgical evaluation. Eyes-closed resting-state interictal MEG band power abnormality maps were derived from 70 healthy controls as a normative baseline. MEG abnormality maps were compared to iEEG electrode implantation, with the spatial overlap of iEEG electrode placement and cerebral MEG abnormalities recorded. Finally, we assessed if the implantation of electrodes in abnormal tissue, and subsequent resection of the strongest abnormalities determined by MEG and iEEG corresponded to surgical success. Intracranial electrodes were implanted in brain tissue with the most abnormal MEG findings - in individuals that were seizure-free post-operatively (T=3.9, p=0.003), but not in those who did not become seizure free. The overlap between MEG abnormalities and electrode placement distinguished surgical outcome groups moderately well (AUC=0.68). In isolation, the resection of the strongest abnormalities as defined by MEG and iEEG separated surgical outcome groups well, AUC=0.71, AUC=0.74 respectively. A model incorporating all three features separated surgical outcome groups best (AUC=0.80). Intracranial EEG is a key tool to delineate the EZ and help render individuals seizure-free post-operatively. We showed that data-driven abnormality maps derived from resting-state MEG recordings demonstrate clinical value and may help guide electrode placement in individuals with neocortical epilepsy. Additionally, our predictive model of post-operative seizure-freedom, which leverages both MEG and iEEG recordings, could aid patient counselling of expected outcome.

4.
ACS Nano ; 16(11): 18009-18017, 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36162100

RESUMO

We present a high-throughput method for identifying and characterizing individual nanowires and for automatically designing electrode patterns with high alignment accuracy. Central to our method is an optimized machine-readable, lithographically processable, and multi-scale fiducial marker system─dubbed LithoTag─which provides nanostructure position determination at the nanometer scale. A grid of uniquely defined LithoTag markers patterned across a substrate enables image alignment and mapping in 100% of a set of >9000 scanning electron microscopy (SEM) images (>7 gigapixels). Combining this automated SEM imaging with a computer vision algorithm yields location and property data for individual nanowires. Starting with a random arrangement of individual InAs nanowires with diameters of 30 ± 5 nm on a single chip, we automatically design and fabricate >200 single-nanowire devices. For >75% of devices, the positioning accuracy of the fabricated electrodes is within 2 pixels of the original microscopy image resolution. The presented LithoTag method enables automation of nanodevice processing and is agnostic to microscopy modality and nanostructure type. Such high-throughput experimental methodology coupled with data-extensive science can help overcome the characterization bottleneck and improve the yield of nanodevice fabrication, driving the development and applications of nanostructured materials.

5.
ACS Nano ; 16(2): 2833-2842, 2022 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-35109656

RESUMO

Magnetic field-driven insulating states in graphene are associated with samples of very high quality. Here, this state is shown to exist in monolayer graphene grown by chemical vapor deposition (CVD) and wet transferred on Al2O3 without encapsulation with hexagonal boron nitride (h-BN) or other specialized fabrication techniques associated with superior devices. Two-terminal measurements are performed at low temperature using a GaAs-based multiplexer. During high-throughput testing, insulating properties are found in a 10 µm long graphene device which is 10 µm wide at one contact with an ≈440 nm wide constriction at the other. The low magnetic field mobility is ≈6000 cm2 V-1 s-1. An energy gap induced by the magnetic field opens at charge neutrality, leading to diverging resistance and current switching on the order of 104 with DC bias voltage at an approximate electric field strength of ≈0.04 V µm-1 at high magnetic field. DC source-drain bias measurements show behavior associated with tunneling through a potential barrier and a transition between direct tunneling at low bias to Fowler-Nordheim tunneling at high bias from which the tunneling region is estimated to be on the order of ≈100 nm. Transport becomes activated with temperature from which the gap size is estimated to be 2.4 to 2.8 meV at B = 10 T. Results suggest that a local electronically high quality region exists within the constriction, which dominates transport at high B, causing the device to become insulating and act as a tunnel junction. The use of wet transfer fabrication techniques of CVD material without encapsulation with h-BN and the combination with multiplexing illustrates the convenience of these scalable and reasonably simple methods to find high quality devices for fundamental physics research and with functional properties.

6.
Commun Biol ; 4(1): 83, 2021 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-33469163

RESUMO

Whole genome duplication (WGD) has occurred in relatively few sexually reproducing invertebrates. Consequently, the WGD that occurred in the common ancestor of horseshoe crabs ~135 million years ago provides a rare opportunity to decipher the evolutionary consequences of a duplicated invertebrate genome. Here, we present a high-quality genome assembly for the mangrove horseshoe crab Carcinoscorpius rotundicauda (1.7 Gb, N50 = 90.2 Mb, with 89.8% sequences anchored to 16 pseudomolecules, 2n = 32), and a resequenced genome of the tri-spine horseshoe crab Tachypleus tridentatus (1.7 Gb, N50 = 109.7 Mb). Analyses of gene families, microRNAs, and synteny show that horseshoe crabs have undergone three rounds (3R) of WGD. Comparison of C. rotundicauda and T. tridentatus genomes from populations from several geographic locations further elucidates the diverse fates of both coding and noncoding genes. Together, the present study represents a cornerstone for improving our understanding of invertebrate WGD events on the evolutionary fates of genes and microRNAs, at both the individual and population level. We also provide improved genomic resources for horseshoe crabs, of applied value for breeding programs and conservation of this fascinating and unusual invertebrate lineage.


Assuntos
Duplicação Gênica/genética , Caranguejos Ferradura/genética , MicroRNAs/genética , Animais , Evolução Molecular , Genoma/genética , Genômica , Filogenia
7.
Science ; 371(6528)2021 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-33509998

RESUMO

Spectroscopic analysis is one of the most widely used analytical tools in scientific research and industry. Although laboratory benchtop spectrometer systems offer superlative resolution and spectral range, their miniaturization is crucial for applications where portability is paramount or where in situ measurements must be made. Advancement in this field over the past three decades is now yielding microspectrometers with performance and footprint near those viable for lab-on-a-chip systems, smartphones, and other consumer technologies. We summarize the technologies that have emerged toward achieving these aims-including miniaturized dispersive optics, narrowband filter systems, Fourier transform interferometers, and reconstructive microspectrometers-and discuss the challenges associated with improving spectral resolution while device dimensions shrink ever further.

8.
PLoS Biol ; 18(9): e3000636, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32991578

RESUMO

The Myriapoda, composed of millipedes and centipedes, is a fascinating but poorly understood branch of life, including species with a highly unusual body plan and a range of unique adaptations to their environment. Here, we sequenced and assembled 2 chromosomal-level genomes of the millipedes Helicorthomorpha holstii (assembly size = 182 Mb; shortest scaffold/contig length needed to cover 50% of the genome [N50] = 18.11 Mb mainly on 8 pseudomolecules) and Trigoniulus corallinus (assembly size = 449 Mb, N50 = 26.78 Mb mainly on 17 pseudomolecules). Unique genomic features, patterns of gene regulation, and defence systems in millipedes, not observed in other arthropods, are revealed. Both repeat content and intron size are major contributors to the observed differences in millipede genome size. Tight Hox and the first loose ecdysozoan ParaHox homeobox clusters are identified, and a myriapod-specific genomic rearrangement including Hox3 is also observed. The Argonaute (AGO) proteins for loading small RNAs are duplicated in both millipedes, but unlike in insects, an AGO duplicate has become a pseudogene. Evidence of post-transcriptional modification in small RNAs-including species-specific microRNA arm switching-providing differential gene regulation is also obtained. Millipedes possesses a unique ozadene defensive gland unlike the venomous forcipules found in centipedes. We identify sets of genes associated with the ozadene that play roles in chemical defence as well as antimicrobial activity. Macro-synteny analyses revealed highly conserved genomic blocks between the 2 millipedes and deuterostomes. Collectively, our analyses of millipede genomes reveal that a series of unique adaptations have occurred in this major lineage of arthropod diversity. The 2 high-quality millipede genomes provided here shed new light on the conserved and lineage-specific features of millipedes and centipedes. These findings demonstrate the importance of the consideration of both centipede and millipede genomes-and in particular the reconstruction of the myriapod ancestral situation-for future research to improve understanding of arthropod evolution, and animal evolutionary genomics more widely.


Assuntos
Adaptação Biológica/genética , Artrópodes , Evolução Molecular , Genoma/genética , Animais , Artrópodes/classificação , Artrópodes/genética , Sequência de Bases , Elementos de DNA Transponíveis/genética , Genes Homeobox , Genoma de Inseto , Insetos/classificação , Insetos/genética , MicroRNAs/genética , Filogenia , Sintenia
9.
Sci Adv ; 6(33): eaba5029, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32851166

RESUMO

Recent advances in inkjet printing of two-dimensional (2D) crystals show great promise for next-generation printed electronics development. Printing nonuniformity, however, results in poor reproducibility in device performance and remains a major impediment to their large-scale manufacturing. At the heart of this challenge lies the coffee-ring effect (CRE), ring-shaped nonuniform deposits formed during postdeposition drying. We present an experimental study of the drying mechanism of a binary solvent ink formulation. We show that Marangoni-enhanced spreading in this formulation inhibits contact line pinning and deforms the droplet shape to naturally suppress the capillary flows that give rise to the CRE. This general formulation supports uniform deposition of 2D crystals and their derivatives, enabling scalable and even wafer-scale device fabrication, moving them closer to industrial-level additive manufacturing.

10.
Science ; 365(6457): 1017-1020, 2019 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-31488686

RESUMO

Spectrometers with ever-smaller footprints are sought after for a wide range of applications in which minimized size and weight are paramount, including emerging in situ characterization techniques. We report on an ultracompact microspectrometer design based on a single compositionally engineered nanowire. This platform is independent of the complex optical components or cavities that tend to constrain further miniaturization of current systems. We show that incident spectra can be computationally reconstructed from the different spectral response functions and measured photocurrents along the length of the nanowire. Our devices are capable of accurate, visible-range monochromatic and broadband light reconstruction, as well as spectral imaging from centimeter-scale focal planes down to lensless, single-cell-scale in situ mapping.

11.
JMIR Serious Games ; 7(2): e11909, 2019 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-30990461

RESUMO

BACKGROUND: Trauma-focused cognitive behavioral therapy (TF-CBT) is a first-line treatment for posttraumatic stress disorder (PTSD). Despite a solid evidence base, TF-CBT response and attrition rates vary considerably. Plasticity-focused interventions, including the use of serious games, have the potential to improve TF-CBT response and treatment retention. OBJECTIVE: The aim of this study was to assess the acceptability of a mobile phone-delivered plasticity-focused serious game to improve response to TF-CBT for PTSD, and carry out a user requirements analysis should the development of a prototype be warranted. METHODS: We conducted 2 one-to-one interviews (n=2), one focus group involving service users who had received a diagnosis of PTSD (n=3) and one focus group involving psychological trauma service clinicians (n=4). RESULTS: We found that the concept of a plasticity-focused mobile phone intervention for PTSD is acceptable to patients and clinicians. Service users and clinicians both believed that the usage should be guided by a therapist, and both contributed useful inputs regarding the audiovisual aspects of the proposed serious game. It was accepted that the game would not be suitable for all patients and that clinicians would need to appropriately prescribe the usage of the game. CONCLUSIONS: The findings highlight the acceptability of the proposed serious game and clarify the user requirements for such an intervention. It is the intention of the authors to carry out a user experience evaluation using a prototype serious game in a clinical population.

12.
Opt Express ; 26(10): 12506-12513, 2018 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-29801288

RESUMO

We demonstrate a long-term stable, all-fiber, erbium-doped femtosecond laser mode-locked by a black phosphorus saturable absorber. The saturable absorber, fabricated by scalable and highly controllable inkjet printing technology, exhibits strong nonlinear optical response and is stable for long-term operation against intense irradiation, overcoming a key drawback of this material. The oscillator delivers self-starting, 102 fs stable pulses centered at 1555 nm with 40 nm spectral bandwidth. This represents the shortest pulse duration achieved from black phosphorus in a fiber laser to date. Our results demonstrate the great potential for black phosphorus as an excellent candidate for long-term stable ultrashort pulse generation.

13.
Sci Rep ; 8(1): 2738, 2018 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-29426938

RESUMO

Ultrafast lasers with tunable parameters in wavelength and time domains are the choice of light source for various applications such as spectroscopy and communication. Here, we report a wavelength and pulse-duration tunable mode-locked Erbium doped fiber laser with single wall carbon nanotube-based saturable absorber. An intra-cavity tunable filter is employed to continuously tune the output wavelength for 34 nm (from 1525 nm to 1559 nm) and pulse duration from 545 fs to 6.1 ps, respectively. Our results provide a novel light source for various applications requiring variable wavelength or pulse duration.

14.
Opt Lett ; 42(18): 3518-3521, 2017 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-28914890

RESUMO

We demonstrate a compact, all-fiber-integrated laser system that delivers Raman solitons with a duration of ∼100 fs and pulse energy of up to 13.3 nJ, continuously wavelength tunable from 1.98 to 2.29 µm via Raman-induced soliton self-frequency shift (SSFS) in a thulium-doped fiber amplifier. We realize a >90% efficiency of Raman conversion, the highest reported value from SSFS-based sources, to the best of our knowledge. This enables us to achieve >10 nJ soliton energy from a 2.16 to 2.29 µm range, the highest energy demonstrated above 2.22 µm from an SSFS-assisted, all-fiber tunable single-soliton-pulse source, to the best of our knowledge. Our simple and compact all-fiber tunable laser could serve as an efficient ∼2 µm femtosecond source for a wide range of mid-infrared applications.

15.
Nat Commun ; 8(1): 278, 2017 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-28819184

RESUMO

Black phosphorus is a two-dimensional material of great interest, in part because of its high carrier mobility and thickness dependent direct bandgap. However, its instability under ambient conditions limits material deposition options for device fabrication. Here we show a black phosphorus ink that can be reliably inkjet printed, enabling scalable development of optoelectronic and photonic devices. Our binder-free ink suppresses coffee ring formation through induced recirculating Marangoni flow, and supports excellent consistency (< 2% variation) and spatial uniformity (< 3.4% variation), without substrate pre-treatment. Due to rapid ink drying (< 10 s at < 60 °C), printing causes minimal oxidation. Following encapsulation, the printed black phosphorus is stable against long-term (> 30 days) oxidation. We demonstrate printed black phosphorus as a passive switch for ultrafast lasers, stable against intense irradiation, and as a visible to near-infrared photodetector with high responsivities. Our work highlights the promise of this material as a functional ink platform for printed devices.Atomically thin black phosphorus shows promise for optoelectronics and photonics, yet its instability under environmental conditions and the lack of well-established large-area synthesis protocols hinder its applications. Here, the authors demonstrate a stable black phosphorus ink suitable for printed ultrafast lasers and photodetectors.

16.
ACS Omega ; 2(6): 2630-2638, 2017 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31457604

RESUMO

Solution processing-based fabrication techniques such as liquid phase exfoliation may enable economically feasible utilization of graphene and related nanomaterials in real-world devices in the near future. However, measurement of the thickness of the thin film structures fabricated by these approaches remains a significant challenge. By using surface plasmon resonance (SPR), a simple, accurate, and quick measurement of the deposited thickness for inkjet-printed graphene thin films is reported here. We show that the SPR technique is convenient and well-suited for the measurement of thin films formulated from nanomaterial inks, even at sub-10 nm thickness. We also demonstrate that the analysis required to obtain results from the SPR measurements is significantly reduced compared to that required for atomic force microscopy (AFM) or stylus profilometer, and much less open to interpretation. The gathered data implies that the film thickness increases linearly with increasing number of printing repetitions. In addition, SPR also reveals the complex refractive index of the printed thin films composed of exfoliated graphene flakes, providing a more rigorous explanation of the optical absorption than that provided by a combination of AFM/profilometer and the extinction coefficient of mechanically exfoliated graphene flakes. Our results suggest that the SPR method may provide a new pathway for the thickness measurement of thin films fabricated from any nanomaterial containing inks.

17.
Nurs Stand ; 30(49): 65, 2016 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-27484570

RESUMO

With her team of unsung heroes at Sandwell General Hospital in the West Midlands, Kelly carries out sterling work in the aftercare of patients with bowel cancer, rectal cancer and other debilitating aspects of incontinence.


Assuntos
Neoplasias do Colo/enfermagem , Relações Enfermeiro-Paciente , Pacientes/psicologia , Incontinência Urinária/enfermagem , Feminino , Humanos , Reino Unido
18.
Stud Health Technol Inform ; 194: 82-7, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23941935

RESUMO

With the growing population with chronic disease in most developed countries, the amount and variety of interactive medical devices adopted in healthcare and wellbeing management is on the rise. Studies show that people with chronic conditions are facing many barriers to effective self-management, which leads to significant economic losses in many countries. The question as to how we can design personal medical devices that are able to facilitate an effective self-management by tackling these barriers presents a challenging research topic. We offer an overview of a controlled-experiment designed to evaluate an innovative tagging feature and a confidence of measurement feature in chronic disease management. This is a work-in-progress, which will finish by the end of June 2013.


Assuntos
Doença Crônica/terapia , Participação do Paciente/métodos , Assistência Centrada no Paciente/métodos , Autocuidado/métodos , Software , Telemedicina/métodos , Interface Usuário-Computador , Ergonomia/métodos , Humanos , Internacionalidade , Design de Software
19.
PLoS One ; 8(4): e60148, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23577087

RESUMO

Maintenance of embryonic stem cell (ESC) self-renewal and pluripotency are controlled by extrinsic factors, molecular signaling pathways and transcriptional regulators. While many of the key players have been studied in depth, how the molecular signals interact with transcription factors of the pluripotency network to regulate their action remains less well understood. Inhibition of glycogen synthase kinase 3 (Gsk-3) has been implicated in the maintenance of mouse ESC pluripotency, although there is contradictory data on its role, with enhancement of cell survival and metabolism, stabilisation of c-Myc and activation of Wnt signalling proposed as potential mechanisms. We have discovered that suppression of Gsk-3 activity leads to enhanced protein levels of key transcriptional regulators of the pluripotency network, notably Nanog, Tbx3 and c-Myc. Protein stability was unchanged following Gsk-3 inhibition, although interestingly, Nanog and Tbx3 proteins were found to have half-lives of 1-3 h, while that of Oct4 protein was longer, at 6 h. We demonstrate that the effects on protein levels seen following inhibition of Gsk-3 are due to both enhanced de novo synthesis of Nanog protein and increases in the proportion of Nanog and Tbx3 RNAs bound to polysomes, findings consistent with Gsk-3 regulating translation of these factors. These effects were not due to changes in regulators of general translation initiation machinery nor mediated via the 5' or 3' UTR sequences of Nanog alone. The data we present provide both new conceptual insight into the mechanisms regulated by Gsk-3 that may contribute to ESC self-renewal and, importantly, establish control of protein translation as an additional mechanism involved in modulation of ESC pluripotency.


Assuntos
Células-Tronco Embrionárias/citologia , Quinase 3 da Glicogênio Sintase/antagonistas & inibidores , Células-Tronco Pluripotentes/citologia , Biossíntese de Proteínas/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Fatores de Transcrição/biossíntese , Animais , Diferenciação Celular/efeitos dos fármacos , Células-Tronco Embrionárias/efeitos dos fármacos , Células-Tronco Embrionárias/metabolismo , Quinase 3 da Glicogênio Sintase/metabolismo , Proteínas de Homeodomínio/genética , Camundongos , Proteína Homeobox Nanog , Células-Tronco Pluripotentes/efeitos dos fármacos , Células-Tronco Pluripotentes/metabolismo , Polirribossomos/efeitos dos fármacos , Polirribossomos/metabolismo , Transdução de Sinais/efeitos dos fármacos
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