485 research outputs found

    The ribosomal protein RACK1 is required for microRNA function in both C. elegans and humans

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    Despite the importance of microRNAs (miRNAs) in gene regulation, it is unclear how the miRNA-Argonaute complex-or miRNA-induced silencing complex (miRISC)-can regulate the translation of their targets in such diverse ways. We demonstrate here a direct interaction between the miRISC and the ribosome by showing that a constituent of the eukaryotic 40S subunit, receptor for activated C-kinase (RACK1), is important for miRNA-mediated gene regulation in animals. In vivo studies demonstrate that RACK1 interacts with components of the miRISC in nematodes and mammals. In both systems, the alteration of RACK1 expression alters miRNA function and impairs the association of the miRNA complex with the translating ribosomes. Our data indicate that RACK1 can contribute to the recruitment of miRISC to the site of translation, and support a post-initiation mode of miRNA-mediated gene repression. © 2011 European Molecular Biology Organization

    Strength-endurance training reduces the hamstrings strength decline following simulated football competition in female players

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    Hamstring strains are the most common injury in multiple sprint sports, with inadequate eccentric hamstring strength and fatigue identified as important risk factors. Resistance training interventions aimed at reducing injury risk typically focus on the development of maximum strength, while little is known about the impact of training on hamstring fatigue resistance. The present study compared the effects of strength endurance (SE) with a strength intervention (S) on the eccentric hamstring strength decline induced by a simulated soccer match. Twenty-one female soccer players were randomly assigned to a S group (n = 10) or a SE group (n = 11). Hamstrings and quadriceps isokinetic concentric and eccentric peak torque (PT) were assessed at 120°.s-1 and hamstrings-to-quadriceps ratio (HEcc:QCon) calculated, pre- and immediately post a 90-min simulated match (BEAST90). This was repeated following a 7-week intervention of either three to five sets of 6RM leg curl and stiff-leg deadlift with 3-min inter-set rest (S), or the same exercises performed using three sets of 12–20 RM with 45–90 s inter-set rest (SE). At baseline, the simulated match led to significant declines in hamstrings eccentric peak torque (EccPT) in both groups in both dominant (D) and non-dominant (ND) legs [SE: (D: −15.5, ND: −15.6%), P = 0.001 to 0.016; S: (D: −12.3%, ND: −15.5%), P = 0.001 to 0.018]. After the 7-week intervention, we observed a group*intervention*match interaction such that there was no significant decline in EccPT in the SE group following the simulated match (D: 5.3%, ND: 2.0%), but there remained significant declines in the S group (D: −14.2%, ND: −15.5%, P = 0.018–0.001). Similarly, in the SE group, there was a significant decrease in the HEcc:QCon in D before (−14.2%, P = 0.007), but not after the training intervention, whereas declines were observed in the S group both at baseline, and following the intervention (D: −13.9%, ND: −15.6%, P = 0.045). These results demonstrate that SE training can reduce the magnitude of the EccPT decline observed during soccer competition. As inadequate eccentric strength and fatigue are both risk factors for hamstring injury, SE training should be considered along with the development of peak eccentric strength, as a component of programs aimed at reducing injury risk in multiple-sprint sports

    Proximal ischemia is a frequent cause of exercise-induced pain in patients with a normal ankle to brachial index at rest

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    BACKGROUND: Excluding a vascular origin of exercise-related pain is often difficult in clinical practice. Recent papers have underlined the frequent association of concurrent lumbar spine degenerative disease and peripheral arterial disease. Furthermore, even when suspected, isolated exercise-induced proximal ischemia is difficult to diagnose. Measurement of transcutaneous oxygen pressure (tcpO2) is an interesting and accurate method to differentiate proximal (buttock) from distal (calf) regional blood flow impairment (RBFI) during exercise. OBJECTIVES: We searched for isolated proximal-without-distal RBFI as a possible cause of claudication, in patients with borderline (ABI-b: 0.91 - 0.99) or normal (ABI-n: 1.00 to 1.40) ankle to brachial index at rest. STUDY DESIGN: Retrospective cohort design study. We analyzed patients referred to our laboratory with symptom limiting claudication and an ankle brachial index within normal limits. SETTING: University-based exercise-investigation center. METHODS: Over a 12-year period, we identified 463 patients referred to our laboratory that had their lowest resting ABI between 0.90 and 1.40. The tcpO2 on chest, buttocks, and calves were recorded during treadmill walking tests (3.2 km/h, 10% slope) in 220 ABI-b and 243 ABI-n unique consecutive patients complaining of limiting claudication (each patient\u27s ABI was the lowest of the 2 legs). Limiting claudication was defined as the reported inability to walk 1 kilometer without stopping. A DROP index (limb tcpO2-changes minus chest tcpO2-changes from rest) below -15 mmHg was used to indicate a positive result (i.e. exercise-induced RBFI). RESULTS: Treadmill exercise showed evidence for proximal or distal RBFI, of at least one side, in 128 out of 220 patients (58.2%) and in 86 out of 243 (35.4%) patients with ABI-b and ABI-n, respectively. Isolated proximal-without-distal RBFI was found in 32 out of the 128 (25.0 %) positive tests in ABI-b and 32 out of the 86 (37.2%) positive tests in ABI-n patients. LIMITATIONS: Study limitations include the absence of systematic follow-up of diagnosed patients and absence of systematic search for cardio-respiratory co-morbid conditions. CONCLUSION: Isolated proximal-without distal RBFI is found in approximately one out of 7 patients complaining of symptom limiting claudication with a borderline or normal resting ABI. Exercise-tcpO2 may help to discriminate patients with arterial claudication that could benefit from invasive vascular investigations and procedures

    Almacén y centro de distribución de materiales de construcción, en Bussigny (Suiza)

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    Centre for storage and distribution of construction material at Bussigny, Switzerland Owing to the cost and small area of the site the building has been extended upwards. The ground floor has access ramps to the various floors, a hall, offices, retail sales department, loading wharfs, etc. The second floor is level with the railway, and on the south east there is a loading platform for heavy trucks. The third floor serves mainly as storage of stocks of light weight materials. Finally, on the top floor, in addition to a car park, there are management offices. The sober and sincerely expressive design and use of materials constitute outstanding aspects of this building.<br><br>El edificio se ha desarrollado en vertical, debido al elevado precio de los solares y al poco espacio disponible. La planta baja contiene, además de las rampas de acceso a las diferentes plantas, el hall; oficinas; sección de venta al detall; muelles de carga; etc. La primera planta, situada al nivel de la vía férrea, dispone al sudeste de un muelle de carga accesible a los vehículos pesados. La segunda planta sirve principalmente para el almacenaje y formación de los stocks de materiales ligeros. Y finalmente, la planta de cubierta, además del parking para los coches, alberga las oficinas de la administración, etc. El tratamiento sobrio del edificio y la sinceridad expresiva de los materiales son las notas destacadas de esta construcción

    Almacén y centro de distribución de materiales de construcción, en Bussigny (Suiza)

    Get PDF
    Centre for storage and distribution of construction material at Bussigny, Switzerland Owing to the cost and small area of the site the building has been extended upwards. The ground floor has access ramps to the various floors, a hall, offices, retail sales department, loading wharfs, etc. The second floor is level with the railway, and on the south east there is a loading platform for heavy trucks. The third floor serves mainly as storage of stocks of light weight materials. Finally, on the top floor, in addition to a car park, there are management offices. The sober and sincerely expressive design and use of materials constitute outstanding aspects of this building.El edificio se ha desarrollado en vertical, debido al elevado precio de los solares y al poco espacio disponible. La planta baja contiene, además de las rampas de acceso a las diferentes plantas, el hall; oficinas; sección de venta al detall; muelles de carga; etc. La primera planta, situada al nivel de la vía férrea, dispone al sudeste de un muelle de carga accesible a los vehículos pesados. La segunda planta sirve principalmente para el almacenaje y formación de los stocks de materiales ligeros. Y finalmente, la planta de cubierta, además del parking para los coches, alberga las oficinas de la administración, etc. El tratamiento sobrio del edificio y la sinceridad expresiva de los materiales son las notas destacadas de esta construcción

    Variability of protistan and bacterial communities in two Arctic fjords (Spitsbergen)

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    Krossfjorden and Kongsfjorden are Arctic fjords on the western side of Spitsbergen. These fjords share a common mouth to the open sea, and both are influenced by the input of sediment-rich glacial meltwater leading to decreased surface salinity, increased turbidity and decreased light penetration during summer. Earlier classical taxonomic studies had described the pelagic protistan composition of the Kongsfjorden during summer, revealing the dominance of flagellates of often unresolved taxonomic origin. Only little information existed on microbial eukaryote composition of the Krossfjorden as well as the bacterial composition of both fjords. The aim of the present study was to analyze and compare surface summertime protistan and bacterial communities in both fjords, using molecular approaches (16S and 18S rRNA DGGE, sequencing). Samples were collected three times a week from the central Kongsfjorden over a 1-month period. Additionally, 10 marine and 2 freshwater sites were sampled within a 1-week period in both Kongsfjorden and Krossfjorden. The central Kongsfjorden revealed a relatively stable protistan community over time with dinoflagellates, chlorophytes and small heterotrophs dominating. In contrast, the bacterial community varied over time and appeared to be correlated with the inflow of glacial meltwater. The Kongsfjorden and Krossfjorden were found to harbor distinctive bacterial and eukaryotic communities. We speculate that differences in glacial meltwater composition and fjord bathymetry affect the surface water properties and therefore the observed spatial variability in the community fingerprints.</p

    RIPK1 protects from TNF-α-mediated liver damage during hepatitis

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    Cell death of hepatocytes is a prominent characteristic in the pathogenesis of liver disease, while hepatolysis is a starting point of inflammation in hepatitis and loss of hepatic function. However, the precise molecular mechanisms of hepatocyte cell death, the role of the cytokines of hepatic microenvironment and the involvement of intracellular kinases, remain unclear. Tumor necrosis factor alpha (TNF-alpha) is a key cytokine involved in cell death or survival pathways and the role of RIPK1 has been associated to the TNF-alpha-dependent signaling pathway. We took advantage of two different deficient mouse lines, the RIPK1 kinase dead knock-in mice (Ripk1K45A) and the conditional knockout mice lacking RIPK1 only in liver parenchymal cells (Ripk1LPC-KO), to characterize the role of RIPK1 and TNF-alpha in hepatitis induced by concanavalin A (ConA). Our results show that RIPK1 is dispensable for liver homeostasis under steady-state conditions but in contrast, RIPK1 kinase activity contributes to caspase-independent cell death induction following ConA injection and RIPK1 also serves as a scaffold, protecting hepatocytes from massive apoptotic cell death in this model. In the Ripk1LPC-KO mice challenged with ConA, TNF-alpha triggers apoptosis, responsible for the observed severe hepatitis. Mechanism potentially involves both TNF-independent canonical NF-kappa B activation, as well as TNF-dependent, but canonical NF-kappa B-independent mechanisms. In conclusion, our results suggest that RIPK1 kinase activity is a pertinent therapeutic target to protect liver against excessive cell death in liver diseases

    El conocimiento del profesor de Matemáticas en la práctica: enseñanza de la proporcionalidad.

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    El papel del profesor de Matemáticas como gestor del proceso de construcción del razonamiento proporcional tiene una especial relevancia; por ello nos planteamos investigar los conocimientos de Matemáticas que el profesor moviliza en la práctica docente en lo que concierne a la temática específica de proporcionalidad en Sexto curso de Primaria y en Primer curso de Secundaria. Este trabajo, centrado en el conocimiento matemático sobre proporcionalidad del profesor, pretende comparar los conocimientos de los profesores de enseñanza Primaria y Secundaria en lo que respecta a la proporcionalidad. El objetivo no es sólo el de comparar los conocimientos matemáticos del profesor sobre proporcionalidad, sino el de observar y analizar cómo enseña dichos contenidos con la finalidad de explicar cuáles son los objetivos que se plantea y cómo promueve la construcción del  concepto matemático de proporcionalidad
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