RESUMEN
This study surveyed awareness of, and adherence to, six national fall prevention recommendations among community-dwelling older adults (n = 1050) in Ottawa. Although 76 per cent of respondents agreed falling is a concern and preventable, fewer perceived susceptibility to falling (63%). Respondents had high awareness that home modifications and physical activity can prevent falls. Reported modifications included grab bars (50%), night lights (44%), and raised toilet seats (19%). Half met aerobic activity recommendations; 38 per cent met strength recommendations. Respondents had lower awareness that an annual medication review, annual eye and physical examination, and daily vitamin D supplementation could reduce fall risk. However, reported annual medication review (79%) and eye examination (75%) was high. Nearly half met recommendations for vitamin D intake. These findings suggest a gap in knowledge of awareness and adherence to national recommendations, highlighting the ones that may require attention from those who work to prevent falls.
Asunto(s)
Accidentes por Caídas/prevención & control , Accidentes Domésticos/prevención & control , Evaluación Geriátrica , Conocimientos, Actitudes y Práctica en Salud , Vida Independiente/psicología , Anciano , Anciano de 80 o más Años , Canadá , Ejercicio Físico , Femenino , Humanos , Vida Independiente/estadística & datos numéricos , Masculino , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
Unlike orthoretroviruses, foamy retroviruses (FV) synthesize Pol independently of Gag. The FV Pol precursor is cleaved only once between reverse transcriptase (RT) and integrase (IN) by the protease (PR), resulting in a PR-RT and an IN protein. Only the Pol precursor, not the cleaved subunits, is packaged into virions. Like orthoretroviral PRs, FV PR needs to dimerize to be active. Previously, we showed that a Pol mutant lacking IN has defects in PR activity and Pol packaging into virions. We now show that introduction of a leucine zipper (zip) dimerization motif in an IN truncation mutant can restore PR activity, leading to Pol processing in cells. However, these zip mutants neither cleave Gag nor incorporate Pol into virions. We propose that IN is required for Pol dimerization, which is necessary for the creation of a functional PR active site.
Asunto(s)
Productos del Gen pol/metabolismo , Integrasas/química , Péptido Hidrolasas/metabolismo , Virus Espumoso de los Simios/enzimología , Animales , Dominio Catalítico , Línea Celular , Activación Enzimática , Productos del Gen pol/química , Productos del Gen pol/genética , Genes pol , Humanos , Integrasas/genética , Integrasas/metabolismo , Leucina Zippers , Mutación , Multimerización de Proteína , Virus Espumoso de los Simios/genética , Virus Espumoso de los Simios/metabolismoRESUMEN
Expression of Mpl is restricted to hematopoietic cells in the megakaryocyte lineage and to undifferentiated progenitors, where it initiates critical cell survival and proliferation signals after stimulation by its ligand, thrombopoietin (TPO). As a result, a deficiency in Mpl function in patients with congenital amegakaryocytic thrombocytopenia (CAMT) and in mpl(-/-) mice produces profound thrombocytopenia and a severe stem cell-repopulating defect. Gene therapy has the potential to correct the hematopoietic defects of CAMT by ectopic gene expression that restores normal Mpl receptor activity. We rescued the mpl(-/-) mouse with a transgenic vector expressing mpl from the promoter elements of the 2-kb region of DNA just proximal to the natural gene start site. Transgene rescued mice exhibit thrombocytosis but only partial correction of the stem cell defect. Furthermore, they show very low-level expression of Mpl on platelets and megakaryocytes, and the transgene-rescued megakaryocytes exhibit diminished TPO-dependent kinase phosphorylation and reduced platelet production in bone marrow chimeras. Thrombocytosis is an unexpected consequence of reduced Mpl expression and activity. However, impaired TPO homeostasis in the transgene-rescued mice produces elevated plasma TPO levels, which serves as an unchecked stimulus to drive the observed excessive megakaryocytopoiesis.
Asunto(s)
Receptores de Trombopoyetina/genética , Receptores de Trombopoyetina/metabolismo , Trombocitosis/patología , Trombocitosis/fisiopatología , Trombopoyesis/fisiología , Animales , Células de la Médula Ósea/citología , Células de la Médula Ósea/fisiología , Diferenciación Celular/fisiología , Dosificación de Gen , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/fisiología , Homeostasis/fisiología , Megacariocitos/citología , Megacariocitos/fisiología , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Transducción de Señal/fisiología , Trombopoyetina/metabolismo , Transgenes/fisiologíaRESUMEN
Foamy viruses (FV) comprise a subfamily of retroviruses. Orthoretroviruses, such as human immunodeficiency virus type 1, synthesize Gag and Pol from unspliced genomic RNA. However, FV Pol is expressed from a spliced mRNA independently of Gag. FV pol splicing uses a 3' splice site located at the 3' end of gag, resulting in a shared exon between gag and pol. Previously, our laboratory showed that C-terminal Gag premature termination codon (PTC) mutations in the 3' shared exon led to greatly decreased levels of Pol protein (C. R. Stenbak and M. L. Linial, J. Virol. 78:9423-9430, 2004). To further characterize these mutants, we quantitated the levels of unspliced gag and spliced pol mRNAs using a real-time PCR assay. In some of the PTC mutants, the levels of spliced pol mRNA were reduced as much as 30-fold, whereas levels of unspliced gag RNA were not affected. Substitutions of a missense codon in place of a PTC restored normal levels of spliced pol mRNA. Disrupting Upf proteins involved in nonsense-mediated mRNA decay (NMD) did not affect Pol protein expression. Introduction of an exonic splicing enhancer downstream of the PTC mutation restored pol splicing to the wild-type level. Taken together, our results show that the PTC mutation itself is responsible for decreased levels of pol mRNA but that mechanisms other than NMD might be involved in downregulating Pol expression. The results also suggest that normal pol splicing utilizes a suboptimal splice site seen for other spliced mRNAs in most retroviruses, in that introduced exonic enhancer elements can increase splicing efficiency.
Asunto(s)
Codón sin Sentido/genética , Productos del Gen gag/metabolismo , Productos del Gen pol/genética , Empalme del ARN/genética , Estabilidad del ARN/genética , Spumavirus/genética , Secuencia de Bases , Línea Celular , Regulación hacia Abajo , Productos del Gen gag/genética , Humanos , Mutación , Mutación Missense , Sitios de Empalme de ARN , ARN Mensajero/metabolismo , ARN Viral/metabolismoRESUMEN
Foamy virus Pol precursor protein processing by the viral protease occurs at only one site, releasing a protease-reverse transcriptase and an integrase protein. To examine whether the cleavage of the Pol precursor protein is necessary for enzymatic activities and efficient viral replication, several mutations were generated around the cleavage site. All cleavage site mutants synthesize wild-type levels of Pol precursor protein. Mutants containing more than two amino acid substitutions around the cleavage site exhibit no detectable Pol processing. The Pol cleavage site is not required for the production of infectious particles in a single round of infection, but is important for subsequent rounds of viral infection. Mutations around the cleavage site affected the enzymatic activities of the protease and reverse transcriptase and prevented replication after two rounds of infection. Interestingly, Pol encapsidation is significantly reduced in some of the mutants.
Asunto(s)
Productos del Gen pol/metabolismo , Spumavirus/fisiología , Replicación Viral , Sustitución de Aminoácidos , Productos del Gen pol/química , Productos del Gen pol/genética , Mutagénesis , Mutación , Péptido Hidrolasas/metabolismo , Precursores de Proteínas/química , Precursores de Proteínas/genética , Precursores de Proteínas/metabolismo , Procesamiento Proteico-Postraduccional , ADN Polimerasa Dirigida por ARN/metabolismo , Origen de Réplica , Spumavirus/genéticaRESUMEN
Crucial aspects of the foamy virus (FV) replication strategy have so far only been investigated for the prototypic FV (PFV) isolate, which is supposed to be derived from nonhuman primates. To study whether the unusual features of this replication pathway also apply to more-distantly related FVs, we constructed feline FV (FFV) infectious molecular clones and vectors. It is shown by quantitative RNA and DNA PCR analysis that FFV virions contain more RNA than DNA. Full-length linear DNA was found in extracellular FFV by Southern blot analysis. Similar to PFV, azidothymidine inhibition experiments and the transfection of nucleic acids extracted from extracellular FFV indicated that DNA is the functional relevant FFV genome. Unlike PFV, no evidence was found indicating that FFV recycles its DNA into the nucleus.