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1.
Mol Metab ; 28: 14-25, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31451430

RESUMO

OBJECTIVE: Glucose-dependent insulinotropic polypeptide (GIP) is secreted from the gut in response to nutrient ingestion and promotes meal-dependent insulin secretion and lipid metabolism. Loss or attenuation of GIP receptor (GIPR) action leads to resistance to diet-induced obesity through incompletely understood mechanisms. The GIPR is expressed in white adipose tissue; however, its putative role in brown adipose tissue (BAT) has not been explored. METHODS: We investigated the role of the GIPR in BAT cells in vitro and in BAT-specific (GiprBAT-/-) knockout mice with selective elimination of the Gipr within the Myf5+ expression domain. We analyzed body weight, adiposity, glucose homeostasis, insulin and lipid tolerance, energy expenditure, food intake, body temperature, and iBAT oxygen consumption ex vivo. High-fat diet (HFD)-fed GiprBAT-/- mice were studied at room temperature (21 °C), 4 °C, and 30 °C ambient temperatures. RESULTS: The mouse Gipr gene is expressed in BAT, and GIP directly increased Il6 mRNA and IL-6 secretion in BAT cells. Additionally, levels of thermogenic, lipid and inflammation mRNA transcripts were altered in BAT cells transfected with Gipr siRNA. Body weight gain, energy expenditure, and glucose and insulin tolerance were normal in HFD-fed GiprBAT-/- mice housed at room temperature. However, GiprBAT-/- mice exhibited higher body temperatures during an acute cold challenge and a lower respiratory exchange ratio and impaired lipid tolerance at 21 °C. In contrast, body weight was lower and iBAT oxygen consumption was higher in HFD-fed mice housed at 4 °C but not at 30 °C. CONCLUSIONS: The BAT GIPR is linked to the control of metabolic gene expression, fuel utilization, and oxygen consumption. However, the selective loss of the GIPR within BAT is insufficient to recapitulate the findings of decreased weight gain and resistance to obesity arising in experimental models with systemic disruption of GIP action.

2.
Endocrinology ; 160(8): 1950-1963, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31237617

RESUMO

Glucagon-like peptide-2 (GLP-2), secreted from enteroendocrine cells, attenuates gut motility, enhances barrier function, and augments nutrient absorption, actions mediated by a single GLP-2 receptor (GLP-2R). Despite extensive analyses, the precise distribution and cellular localization of GLP-2R expression remains controversial, confounded by the lack of suitable GLP-2R antisera. Here, we reassessed murine Glp2r expression using regular and real-time quantitative PCR (qPCR), in situ hybridization (ISH), and a Glp2rLacZ reporter mouse. Glp2r mRNA expression was detected from the stomach to the rectum and most abundant in the jejunum. Glp2r transcripts were also detected in cerebral cortex, mesenteric lymph nodes, gallbladder, urinary bladder, and mesenteric fat. Surprisingly, Glp2r mRNA was found in testis by qPCR at levels similar to jejunum. However, the testis Glp2r transcripts, detected by different primer pairs and qPCR, lacked 5' mRNA coding sequences, and only a minute proportion of them corresponded to full-length Glp2r mRNA. Within the gut, Glp2r-driven LacZ expression was localized to enteric neurons and lamina propria stromal cells, findings confirmed by ISH analysis of the endogenous Glp2r mRNA. Unexpectedly, vascular Glp2rLacZ expression was localized to mesenteric veins and not arteries. Moreover, mesenteric fat Glp2rLacZ expression was detected within blood vessels and not adipocytes. Reporter LacZ expression was not detected in all tissues expressing an endogenous Glp2r transcript, such as gallbladder, urinary bladder, and mesenteric lymph nodes. Collectively, these findings extend our understanding of the cellular domains of Glp2r expression and highlight limitations inherent in application of commonly used technologies to infer analysis of gene expression.

3.
BMC Palliat Care ; 18(1): 39, 2019 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-31027498

RESUMO

BACKGROUND: Internationally, it is widely accepted that holistic care is as an integral part of the care for people with motor neurone disease (MND), and their informal carers. However the optimal role of generalist and specialist palliative care, and how it integrates with specialist neurology services, is not fully established. Using a qualitative approach we sought to examine end of life care for people with MND in Northern Ireland, and the role of specialist and generalist palliative care. METHODS: Qualitative study involving a convenience sample of 13 bereaved carers recruited using the Northern Ireland MND Register. Data collection consisted of semi-structured interviews with the bereaved carers of patients who had died 3-24 months previously with a diagnosis of MND. Data were analysed using thematic analysis. RESULTS: Findings illuminated variations in relation to the levels of holistic care provided to this cohort of patients. Unmanaged respiratory and psychological symptoms caused perceived distress amongst patients. Participants' experiences additionally highlighted reluctance amongst patients with MND to engage with services such as specialist palliative care. Conversely, for those who received input from specialist palliative care services carers portrayed these services to be of great benefit to the patient. CONCLUSIONS: Patients with MND in Northern Ireland may have many unmet holistic care needs. Key areas that require particular focus in terms of service development include neuromuscular respiratory physiotherapy and psychological services for patients. Future research must explore an optimal model of holistic care delivery for patients with MND and how this can be effectively integrated to best meet this patient cohorts palliative care needs.


Assuntos
Cuidadores/psicologia , Cuidados Paliativos na Terminalidade da Vida/métodos , Doença dos Neurônios Motores/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Cuidados Paliativos na Terminalidade da Vida/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Doença dos Neurônios Motores/psicologia , Irlanda do Norte , Cuidados Paliativos/métodos , Cuidados Paliativos/psicologia , Pesquisa Qualitativa
4.
Innovations (Phila) ; 14(2): 177-182, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30885090

RESUMO

Coronary artery disease is often present with aortic stenosis. Although transcatheter aortic valve replacement and minimally invasive surgery provide alternative sternal-sparing options for isolated aortic valve replacement, non-sternotomy treatment of combined coronary artery disease and aortic stenosis has not been well-defined. We report 3 patients who presented with severe aortic stenosis and obstructive coronary artery disease in whom minimally invasive aortic valve replacement using sutureless valve was performed, followed by transradial percutaneous coronary intervention of obstructive coronary lesion. This case series demonstrates a hybrid technique for the treatment of combined severe aortic stenosis and coronary artery disease, which has potential for adequately treating both conditions with minimal risk.

5.
Proc Natl Acad Sci U S A ; 116(9): 3662-3667, 2019 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-30808755

RESUMO

Kaufman oculocerebrofacial syndrome (KOS) is a recessive neurodevelopmental disorder characterized by intellectual disability and lack of speech. KOS is caused by inactivating mutations in UBE3B, but the underlying biological mechanisms are completely unknown. We found that loss of Ube3b in mice resulted in growth retardation, decreased grip strength, and loss of vocalization. The brains of Ube3b -/- mice had hypoplasia of the corpus callosum, enlarged ventricles, and decreased thickness of the somatosensory cortex. Ube3b -/- cortical neurons had abnormal dendritic morphology and synapses. We identified 22 UBE3B interactors and found that branched-chain α-ketoacid dehydrogenase kinase (BCKDK) is an in vivo UBE3B substrate. Since BCKDK targets several metabolic pathways, we profiled plasma and cortical metabolomes from Ube3b -/- mice. Nucleotide metabolism and the tricarboxylic acid cycle were among the pathways perturbed. Substrate-induced mitochondrial respiration was reduced in skeletal muscle but not in liver of Ube3b -/- mice. To assess the relevance of these findings to humans, we identified three KOS patients who had compound heterozygous UBE3B mutations. We discovered changes in metabolites from similar pathways in plasma from these patients. Collectively, our results implicate a disease mechanism in KOS, suggest that it is a metabolic encephalomyopathy, and provide an entry to targeted therapies.


Assuntos
Anormalidades do Olho/genética , Deficiência Intelectual/genética , Transtornos do Desenvolvimento da Linguagem/genética , Deformidades Congênitas dos Membros/genética , Microcefalia/genética , Proteínas Quinases/genética , Ubiquitina-Proteína Ligases/genética , Adolescente , Adulto , Animais , Encéfalo/fisiopatologia , Criança , Anormalidades do Olho/fisiopatologia , Facies , Humanos , Deficiência Intelectual/fisiopatologia , Transtornos do Desenvolvimento da Linguagem/fisiopatologia , Deformidades Congênitas dos Membros/fisiopatologia , Masculino , Redes e Vias Metabólicas , Camundongos , Camundongos Knockout , Microcefalia/fisiopatologia , Mutação , Fenótipo , Ubiquitina/genética
6.
Mol Metab ; 22: 37-48, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30772257

RESUMO

OBJECTIVE: Administration of glucagon (GCG) or GCG-containing co-agonists reduces body weight and increases energy expenditure. These actions appear to be transduced by multiple direct and indirect GCG receptor (GCGR)-dependent mechanisms. Although the canonical GCGR is expressed in brown adipose tissue (BAT) the importance of BAT GCGR activity for the physiological control of body weight, or the response to GCG agonism, has not been defined. METHODS: We studied the mechanisms linking GCG action to acute increases in oxygen consumption using wildtype (WT), Ucp1-/- and Fgf21-/- mice. The importance of basal GCGR expression within the Myf5+ domain for control of body weight, adiposity, glucose and lipid metabolism, food intake, and energy expenditure was examined in GcgrBAT-/- mice housed at room temperature or 4 °C, fed a regular chow diet (RCD) or after a prolonged exposure to high fat diet (HFD). RESULTS: Acute GCG administration induced lipolysis and increased the expression of thermogenic genes in BAT cells, whereas knockdown of Gcgr reduced expression of genes related to thermogenesis. GCG increased energy expenditure (measured by oxygen consumption) both in vivo in WT mice and ex vivo in BAT and liver explants. GCG also increased acute energy expenditure in Ucp1-/- mice, but these actions were partially blunted in Ffg21-/- mice. However, acute GCG administration also robustly increased oxygen consumption in GcgrBAT-/- mice. Moreover, body weight, glycemia, lipid metabolism, body temperature, food intake, activity, energy expenditure and adipose tissue gene expression profiles were normal in GcgrBAT-/- mice, either on RCD or HFD, whether studied at room temperature, or chronically housed at 4 °C. CONCLUSIONS: Exogenous GCG increases oxygen consumption in mice, also evident both in liver and BAT explants ex vivo, through UCP1-independent, FGF21-dependent pathways. Nevertheless, GCGR signaling within BAT is not physiologically essential for control of body weight, whole body energy expenditure, glucose homeostasis, or the adaptive metabolic response to cold or prolonged exposure to an energy dense diet.

7.
Clin Exp Rheumatol ; 2018 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-30148446

RESUMO

OBJECTIVES: The temporal relationship between osteoarthritis and comorbidity is unclear and may vary with socioeconomic status. The aims of this study were to identify if osteoarthritis was associated with onset of common comorbidities, and if the association was moderated by deprivation. METHODS: Prospective cohort study combining questionnaire and medical record data (n=3910). Associations between osteoarthritis and onset of comorbidity at the three-year follow-up were examined using regression models. Interaction terms and stratified analysis were used to examine moderation. RESULTS: Osteoarthritis was associated with onset of all comorbidities (p<0.05). After adjusting for confounders, osteoarthritis was associated with onset of widespread pain (adjusted odds ratio 2.49; 95% confidence interval 1.96-3.17) and insomnia (1.58;1.14-1.19). Interactions between osteoarthritis and change in income and onset cognitive impairment (p=0.047; onset was higher when income became inadequate), and between osteoarthritis and education and onset widespread pain (p=0.012; onset was higher in those with high levels of education) were significant. CONCLUSIONS: Consulters for osteoarthritis were more likely to develop physical and psychological comorbidities than those without osteoarthritis. The moderation analyses indicated that mechanisms to comorbidity differ by socio-economic strata and a need for different approaches to prevent comorbidity for consulters with OA from different levels of deprivation.

8.
Artigo em Inglês | MEDLINE | ID: mdl-28420149

RESUMO

Background: Survival disparities in cancer are known to occur between public and private hospitals. We compared breast cancer presentation, treatment and survival between a public academic hospital and a private hospital in a middle-income country. Methods: The demographics, clinical characteristics, treatment and overall survival (OS) of 2767 patients with invasive breast carcinoma diagnosed between 2001 and 2011 in the public hospital were compared with 1199 patients from the private hospital. Results: Compared to patients in the private hospital, patients from the public hospital were older at presentation, and had more advanced cancer stages. They were also more likely to receive mastectomy and chemotherapy but less radiotherapy. The five-year OS in public patients was significantly lower than in private patients (71.6% vs. 86.8%). This difference was largely attributed to discrepancies in stage at diagnosis and, although to a much smaller extent, to demographic differences and treatment disparities. Even following adjustment for these factors, patients in the public hospital remained at increased risk of mortality compared to their counterparts in the private hospital (Hazard Ratio: 1.59; 95% Confidence Interval: 1.36-1.85). Conclusion: Late stage at diagnosis appears to be a major contributing factor explaining the breast cancer survival disparity between public and private patients in this middle-income setting.


Assuntos
Neoplasias da Mama/patologia , Disparidades em Assistência à Saúde , Hospitais Privados , Hospitais Públicos , Internacionalidade , Análise de Sobrevida , Adulto , Feminino , Humanos , Renda , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais
9.
PLoS One ; 12(3): e0172975, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28296921

RESUMO

BACKGROUND: Breast cancer patients often experience a high level of distress. Psychological distress is a broad construct encompass both depression and anxiety. Previous studies in examining which of these psychological symptoms (either anxiety or depression) were more significantly associated with the distress level in breast cancer patients is lacking. This study aims to compare the level of depression and anxiety between patients with different level of distress. The correlation between the changes in distress level with depression or anxiety over 12 months was also examined. METHODS: This study is from the MyBCC cohort study. Two hundred and twenty one female breast cancer patients were included into the study. They were assessed at the time of diagnosis, 6 months and 12 month using Hospital Anxiety and Depression Scale (HADS) and distress thermometer. The information on age, ethnicity, treatment types and staging of cancer were collected. RESULTS: 50.2%, 51.6% and 40.3% of patients had perceived high level of distress at baseline, 6 months and 1 year after diagnosis. Those with high perceived level of distress had significant higher anxiety scores even after adjusted for the underlying depressive scores (Adjusted OR at baseline = 1.28, 95% CI = 1.13-1.44; adjusted OR at 6 months = 1.27, 95% CI = 1.11-1.45; adjusted OR at 12 months = 1.51, 95% CI = 1.29-1.76). There were no significant differences in the depressive scores between the subjects with either low or high distress level. There was reduction in perceived level of distress, anxiety and depression scores at 12 months after the diagnosis. The decrease of distress was positively correlated with the reduction of anxiety scores but not the changes of depressive scores (r' = 0.25). CONCLUSION: Anxiety is a more significant psychological state that contributed to the feeling of distress in breast cancer as compared with depression. Levels of anxiety at diagnosis in this study would justify screening for anxiety, early identification and therapy for maintaining the psychological well-being of breast cancer patients. Further studies will be needed to measure the effectiveness of therapeutic interventions.


Assuntos
Ansiedade/psicologia , Neoplasias da Mama/psicologia , Depressão/psicologia , Adulto , Feminino , Humanos , Pessoa de Meia-Idade
10.
Artigo em Inglês | MEDLINE | ID: mdl-26473767

RESUMO

Material consistent with knowledge/experience is generally more memorable than material inconsistent with knowledge/experience - an effect that can be more extreme in older adults. Four experiments investigated knowledge effects on memory with young and older adults. Memory for familiar and unfamiliar proverbs (Experiment 1) and for common and uncommon scenes (Experiment 2) showed similar knowledge effects across age groups. Memory for person-consistent and person-neutral actions (Experiment 3) showed a greater benefit of prior knowledge in older adults. For cued recall of related and unrelated word pairs (Experiment 4), older adults benefited more from prior knowledge only when it provided uniquely useful additional information beyond the episodic association itself. The current data and literature suggest that prior knowledge has the age-dissociable mnemonic properties of (1) improving memory for the episodes themselves (age invariant), and (2) providing conceptual information about the tasks/stimuli extrinsically to the actual episodic memory (particularly aiding older adults).


Assuntos
Envelhecimento/psicologia , Rememoração Mental , Recognição (Psicologia) , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Sinais (Psicologia) , Feminino , Humanos , Masculino , Adulto Jovem
11.
J Food Sci Technol ; 51(8): 1429-41, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25114333

RESUMO

This review assesses the nutritional attributes of coarse cereals and also their utilization as food and as formulated foods. These cereals are laden with phytochemicals including phenolic acids, tannins, anthocyanins, phytosterols, avenenathramides and policosanols. They possess high antioxidant properties in vitro than staple cereals and fruits by different purported pathways. There are also some anti-nutritional factors that may be reduced by certain processing treatments. Several epidemiological studies show that these cereals are helpful in reducing several kinds of chronic diseases like cancers, cardiovascular diseases, type II diabetes and various gastrointestinal disorders. Being coarse in nature, they cannot replace our staple cereals, but can be used in different proportions with rice and wheat to formulate various nutritional products. They can be used to make porridges, biscuits, cakes, cookies, tortillas, bread, probiotic drinks, ladoo, ghatta, flakes and several fermented foods. The coarse cereals also have good potential in manufacturing bioethanol, paper, oil and biofilms.

12.
Pathology ; 46(1): 53-9, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24300711

RESUMO

We aimed to streamline the diagnosis of gastrointestinal disease by producing multiplexed real time polymerase chain reaction (PCR) panels employing universal sample processing for DNA and RNA containing pathogens. A total of 487 stored, previously characterised stool samples comprising bacterial, viral, protozoan and Clostridium difficile positive samples were tested using four multiplexed real time PCR panels. A further 81 pre-selected clinical samples from a teaching hospital were included to provide an independent validation of assay performance. Improved sensitivity was achieved using the protozoan panels and 16 more mixed infections were observed compared to tests with conventional methods. Using the C. difficile panels, 100% sensitivity was achieved when compared to the gold standard of toxigenic culture. In addition, hypervirulent strains including ribotype 027 could be identified directly from primary sample without the need for ribotyping methods. Bacterial and viral panels detecting Salmonella, Shigella, Campylobacter, Yersinia enterocolitica, Listeria monocytogenes, norovirus groups I and II, rotavirus A, astrovirus, sapovirus, rotavirus B, adenovirus and adenovirus 40/41 performed as well as conventional methods, whilst allowing detection in 3 hours from processing to result. Multiplex real time PCR panels with universal sample preparation allow streamlined, rapid diagnosis of gastrointestinal pathogens whilst extending the characterisation of pathogens present in stool samples from affected patients.


Assuntos
Bactérias/isolamento & purificação , Gastroenteropatias/diagnóstico , Reação em Cadeia da Polimerase Multiplex/métodos , Parasitos/isolamento & purificação , Vírus/isolamento & purificação , Animais , Bactérias/genética , Clostridium difficile/genética , Clostridium difficile/isolamento & purificação , Fezes/microbiologia , Fezes/parasitologia , Gastroenteropatias/microbiologia , Gastroenteropatias/parasitologia , Humanos , Parasitos/genética , Kit de Reagentes para Diagnóstico , Reação em Cadeia da Polimerase em Tempo Real/métodos , Sensibilidade e Especificidade , Fatores de Tempo , Vírus/genética
13.
Peptides ; 28(4): 893-9, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17267074

RESUMO

Natriuretic peptide receptor-A (NPRA) is the principal receptor for the cardiac hormones ANP and BNP. Mice lacking NPRA develop progressive cardiac hypertrophy and congestive heart failure. However, the mechanisms responsible for hypertrophic growth in the absence of NPRA signaling are not yet known. In the present study, we determined whether deficiency of NPRA/cGMP signaling alters the cardiac pro-inflammatory cytokines gene expression in Npr1 (coding for NPRA) gene-knockout (Npr1(-/-)) mice exhibiting cardiac hypertrophy and fibrosis as compared with control wild-type (Npr1(+/+)) mice. A significant up-regulation of cytokine genes such as TNF-alpha (five-fold), IL-6 (three-fold) and TGF-beta1 (four-fold) were observed in mutant mice hearts lacking NPRA as compared with the age-matched wild-type mice. In parallel, NF-kappaB binding activity was almost five-fold greater in the nuclear extract of Npr1(-/-) mutant mice hearts as compared with wild-type Npr1(+/+) mice hearts. Guanylyl cyclase (GC) activity and cGMP levels were drastically reduced by 10- and 5-fold, respectively, in ventricular tissues of mutant mice hearts relative to wild-type controls. The present findings provide direct evidence that ablation of NPRA/cGMP signaling activates inflammatory cytokines, probably via NF-kappaB mediated signaling pathway, and is associated with hypertrophic growth of null mutant mice hearts.


Assuntos
Citocinas/metabolismo , Guanilato Ciclase/fisiologia , Receptores do Fator Natriurético Atrial/fisiologia , Animais , Northern Blotting , Western Blotting , GMP Cíclico/metabolismo , Citocinas/genética , Ensaio de Desvio de Mobilidade Eletroforética , Deleção de Genes , Regulação da Expressão Gênica , Guanilato Ciclase/genética , Guanilato Ciclase/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Camundongos , Camundongos Knockout , Miocárdio/metabolismo , Miocárdio/patologia , NF-kappa B/genética , NF-kappa B/metabolismo , Oligonucleotídeos/metabolismo , Ligação Proteica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores do Fator Natriurético Atrial/genética , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo
14.
J Biol Chem ; 279(20): 20999-1002, 2004 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-15016812

RESUMO

Reversible covalent modification of proteins with a small ubiquitin-related modifier (SUMO) is emerging as an important system contributing to dynamic regulation of protein function. To enhance our understanding of the cell regulatory systems impacted by sumoylation, we used affinity chromatography-coupled high pressure liquid chromatography/tandem mass spectrometry for unbiased identification of candidate cellular SUMO substrate proteins. Here we describe the identification of 21 candidate sumoylated proteins from whole-cell lysates of HEK-293 cells. The nature of the proteins identified is consistent with a role for sumoylation in diverse cell regulatory systems but highlights regulation of chromatin organization and gene expression as major systems targeted by the sumoylation machinery.


Assuntos
Proteína SUMO-1/química , Proteína SUMO-1/metabolismo , Ubiquitina/metabolismo , Sítios de Ligação , Linhagem Celular , Cromatografia Líquida de Alta Pressão , Humanos , Rim , Espectrometria de Massas , Subunidades Proteicas/química , Subunidades Proteicas/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Especificidade por Substrato , Transfecção
15.
Biochemistry ; 42(26): 7967-75, 2003 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-12834349

RESUMO

RNA interference (RNAi) is proving to be a robust and versatile technique for controlling gene expression in mammalian cells. To fully realize its potential in vivo, however, it may be necessary to introduce chemical modifications to optimize potency, stability, and pharmacokinetic properties. Here, we test the effects of chemical modifications on RNA stability and inhibition of gene expression. We find that RNA duplexes containing either phosphodiester or varying numbers of phosphorothioate linkages are remarkably stable during prolonged incubations in serum. Treatment of cells with RNA duplexes containing phosphorothioate linkages leads to selective inhibition of gene expression. RNAi also tolerates the introduction of 2'-deoxy-2'-fluorouridine or locked nucleic acid (LNA) nucleotides. Introduction of LNA nucleotides also substantially increases the thermal stability of modified RNA duplexes without compromising the efficiency of RNAi. These results suggest that inhibition of gene expression by RNAi is compatible with a broad spectrum of chemical modifications to the duplex, affording a wide range of useful options for probing the mechanism of RNAi and for improving RNA interference in vivo.


Assuntos
Caveolinas/metabolismo , Expressão Gênica , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Western Blotting , Caveolina 1 , Caveolinas/antagonistas & inibidores , Caveolinas/genética , Primers do DNA , Inativação Gênica , Células HeLa , Humanos , RNA Interferente Pequeno/química , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Uridina/análogos & derivados , Uridina/química , Uridina/metabolismo
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