991 research outputs found

    Exploring the association between rDNA dosage and muscular responses to resistance training in young adults

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    Muscle plasticity is affected by physical activity and inactivity, and resistance training has been shown to prevent and reverse negative consequences of inactivity and disuse, such as loss of muscle strength, function, and quality. Ribosomal biogenesis has been shown to be an important factor in understanding the mechanisms behind muscle growth, where total RNA (~ 80-85% rRNA) is an important proxy marker. Resistance training-induced accumulation of total RNA / rRNA has been demonstrated, it is unclear whether the amount of rDNA dose in the genome is decisive for this accumulation. 46 healthy young adults (females: 24.9 (3.8) years; men: 25.0 (4.24) years) were included, and completed 8 weeks of strength training divided into three training modalities, 0 sets (control), 3 sets, and 6 sets; with a training frequency of 3 times/week. Strength tests, ultrasound, DXA scan, blood tests, and muscle biopsy were performed to map physiological, molecular, and, phenotypic changes. A valid qPCR-based method was developed to estimate the rDNA dose in muscle and blood tissues. Total RNA increased significantly from T2 to T3, and an association was found between rDNA dose and exercise-induced accumulated total RNA at T3 (r = 0.470; p = 0.004), but no significant association was found at T2 and post-intervention. rDNA dose did not predict the observed muscle growth measured post-intervention. Contralateral resistance training showed muscular response through increased muscle strength and muscle thickness, but it was not volume-dependent (moderate versus high). In conclusion, rDNA dose appears to be associated with exercise-induced total RNA accretion. More research is needed to determine whether rDNA dose may be a determining factor for resistance training-induced responses to ribosomal biogenesis

    The appreciation of nature and landscape by tourism service providers and visitors in the Ore Mountains (Germany)

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    The paper presents empirical studies on the appreciation of nature and landscape in the Eastern Ore Mountains (Saxony, Germany) by tourism service providers (TSP) and visitors. Attractive landscape and experience of nature are the most important reasons to visit this region and to spend leisure time there. Particularly mountain meadows, raised bogs and mixed forests are highly appreciated. Deforestation, industrial development and the decline of biodiversity would reduce attractiveness for visitors. We also assessed whether the tourism sector is prepared to contribute to the funding of nature conservation and landscape management. Use of general tax revenues is favoured, but other modes would also be accepted, e.g. a nature tax. Willingness to pay (WTP) is ranging between €0.75 and €1.36 per guest per night by TSP, or between €1.06 and €2.73 per day by visitors. With respect to landscape preference and WTP we found in some cases significant differences among visitors, depending on region of residence, age and education level. A major part of the annual costs for nature conservation and landscape could be covered by public funds (taxes), if the results of the WTP approach were understood as a sign of societal demand and a call to action

    A decadal satellite record of gravity wave activity in the lower stratosphere to study polar stratospheric cloud formation

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    Atmospheric gravity waves yield substantial small-scale temperature fluctuations that can trigger the formation of polar stratospheric clouds (PSCs). This paper introduces a new satellite record of gravity wave activity in the polar lower stratosphere to investigate this process. The record is comprised of observations of the Atmospheric Infrared Sounder (AIRS) aboard NASA's Aqua satellite from January 2003 to December 2012. Gravity wave activity is measured in terms of detrended and noise-corrected 15 µm brightness temperature variances, which are calculated from AIRS channels that are the most sensitive to temperature fluctuations at about 17–32 km of altitude. The analysis of temporal patterns in the data set revealed a strong seasonal cycle in wave activity with wintertime maxima at mid- and high latitudes. The analysis of spatial patterns indicated that orography as well as jet and storm sources are the main causes of the observed waves. Wave activity is closely correlated with 30 hPa zonal winds, which is attributed to the AIRS observational filter. We used the new data set to evaluate explicitly resolved temperature fluctuations due to gravity waves in the European Centre for Medium-Range Weather Forecasts (ECMWF) operational analysis. It was found that the analysis reproduces orographic and non-orographic wave patterns in the right places, but that wave amplitudes are typically underestimated by a factor of 2–3. Furthermore, in a first survey of joint AIRS and Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) satellite observations, nearly 50 gravity-wave-induced PSC formation events were identified. The survey shows that the new AIRS data set can help to better identify such events and more generally highlights the importance of the process for polar ozone chemistry

    Kostnadskartlegging av fylkeskommunale fagskoler

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    På oppdrag fra Kunnskapsdepartementet har Deloitte og NIFU kartlagt kostnadene i de fylkeskommunale fagskolene. Hensikten har vært å skaffe oversikt over fylkeskommunenes samlede kostnader til fagskoler, hvordan kostnadene fordeler seg på ulike utdanninger og hva som forklarer kostnadsvariasjon. Kartleggingen er gjort med sikte på å skaffe til veie et faktagrunnlag for et nytt incentivbasert finansieringssystem

    A decadal satellite record of gravity wave activity in the lower stratosphere to study polar stratospheric cloud formation

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    Atmospheric gravity waves yield substantial small-scale temperature fluctuations that can trigger the formation of polar stratospheric clouds (PSCs). This paper introduces a new satellite record of gravity wave activity in the polar lower stratosphere to investigate this process. The record comprises observations of the Atmospheric InfraRed Sounder (AIRS) aboard NASA's Aqua satellite during January 2003 to December 2012. Gravity wave activity is measured in terms of detrended and noise-corrected 15 μm brightness temperature variances, which are calculated from AIRS channels that are most sensitive to temperature fluctuations at about 17–32 km altitude. The analysis of temporal patterns in the data set revealed a strong seasonal cycle in wave activity with wintertime maxima at mid and high latitudes. The analysis of spatial patterns indicated that orography as well as jet and storm sources are the main cause of the observed waves. Wave activity is closely correlated with 30 hPa zonal winds, which is attributed to the AIRS observational filter. We used the new data set to evaluate explicitly resolved temperature fluctuations due to gravity waves in the European Centre for Medium-Range Weather Forecast (ECMWF) operational analysis. It was found that the analysis reproduces orographic and non-orographic wave patterns in the right places, but that wave amplitudes are typically underestimated by a factor of 2–3. Furthermore, in a first survey of joint AIRS and Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) satellite observations nearly 50 gravity wave-induced PSC formation events were identified. The survey shows that the new AIRS data set can help to better identify such events and more generally highlights the importance of the process for polar ozone chemistry

    Long-Term Neuroanatomical Consequences of Childhood Maltreatment: Reduced Amygdala Inhibition by Medial Prefrontal Cortex

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    Similar to patients with Major depressive disorder (MDD), healthy subjects at risk for depression show hyperactivation of the amygdala as a response to negative emotional expressions. The medial prefrontal cortex is responsible for amygdala control. Analyzing a large cohort of healthy subjects, we aimed to delineate malfunction in amygdala regulation by the medial prefrontal cortex in subjects at increased risk for depression, i.e., with a family history of affective disorders or a personal history of childhood maltreatment. We included a total of 342 healthy subjects from the FOR2107 cohort (www.for2107.de). An emotional face-matching task was used to identify the medial prefrontal cortex and right amygdala. Dynamic Causal Modeling (DCM) was conducted and neural coupling parameters were obtained for healthy controls with and without particular risk factors for depression. We assigned a genetic risk if subjects had a first-degree relative with an affective disorder and an environmental risk if subjects experienced childhood maltreatment. We then compared amygdala inhibition during emotion processing between groups. Amygdala inhibition by the medial prefrontal cortex was present in subjects without those two risk factors, as indicated by negative model parameter estimates. Having a genetic risk (i.e., a family history) did not result in changes in amygdala inhibition compared to no risk subjects. In contrast, childhood maltreatment as environmental risk has led to a significant reduction of amygdala inhibition by the medial prefrontal cortex. We propose a mechanistic explanation for the amygdala hyperactivity in subjects with particular risk for depression, in particular childhood maltreatment, caused by a malfunctioned amygdala downregulation via the medial prefrontal cortex. As childhood maltreatment is a major environmental risk factor for depression, we emphasize the importance of this potential early biomarker

    From modular to centralized organization of synchronization in functional areas of the cat cerebral cortex

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    Recent studies have pointed out the importance of transient synchronization between widely distributed neural assemblies to understand conscious perception. These neural assemblies form intricate networks of neurons and synapses whose detailed map for mammals is still unknown and far from our experimental capabilities. Only in a few cases, for example the C. elegans, we know the complete mapping of the neuronal tissue or its mesoscopic level of description provided by cortical areas. Here we study the process of transient and global synchronization using a simple model of phase-coupled oscillators assigned to cortical areas in the cerebral cat cortex. Our results highlight the impact of the topological connectivity in the developing of synchronization, revealing a transition in the synchronization organization that goes from a modular decentralized coherence to a centralized synchronized regime controlled by a few cortical areas forming a Rich-Club connectivity pattern.Comment: 24 pages, 8 figures. Final version published in PLoS On

    Observed and Modeled Mountain Waves from the Surface to the Mesosphere Near the Drake Passage

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    Four state-of-the-science numerical weather prediction (NWP) models were used to perform mountain wave- (MW) resolving hind-casts over the Drake Passage of a 10-day period in 2010 with numerous observed MW cases. The Integrated Forecast System (IFS) and the Icosahedral Nonhydrostatic (ICON) model were run at Δx ≈ 9 and 13 km globally. TheWeather Research and Forecasting (WRF) model and the Met Office Unified Model (UM) were both configured with a Δx = 3 km regional domain. All domains had tops near 1 Pa (z ≈ 80 km). These deep domains allowed quantitative validation against Atmospheric InfraRed Sounder (AIRS) observations, accounting for observation time, viewing geometry, and radiative transfer. All models reproduced observed middle-atmosphere MWs with remarkable skill. Increased horizontal resolution improved validations. Still, all models underrepresented observed MW amplitudes, even after accounting for model effective resolution and instrument noise, suggesting even at Δx ≈ 3 km resolution, small-scale MWs are under-resolved and/or over-diffused. MWdrag parameterizations are still necessary in NWP models at current operational resolutions of Δx ≈ 10 km. Upper GW sponge layers in the operationally configured models significantly, artificially reduced MW amplitudes in the upper stratosphere and mesosphere. In the IFS, parameterized GW drags partly compensated this deficiency, but still, total drags were ≈ 6 time smaller than that resolved at Δx ≈ 3 km. Meridionally propagating MWs significantly enhance zonal drag over the Drake Passage. Interestingly, drag associated with meridional fluxes of zonal momentum (i.e. u'v') were important; not accounting for these terms results in a drag in the wrong direction at and below the polar night jet

    Aberrant Expression of and Cell Death Induction by Engagement of the MHC-II Chaperone CD74 in Anaplastic Large Cell Lymphoma (ALCL)

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    SIMPLE SUMMARY: Anaplastic large cell lymphoma (ALCL) is a lymphoid malignancy considered to be derived from T cells. Currently, two types of systemic ALCL are distinguished: anaplastic lymphoma kinase (ALK)-positive and ALK-negative ALCL. Although ALK(+) and ALK(−) ALCL differ at the genomic and molecular levels, various key biological and molecular features are highly similar between both entities. We have developed the concept that both ALCL entities share a common principle of pathogenesis. In support of this concept, we here describe a common deregulation of CD74, which is usually not expressed in T cells, in ALCL. Ligation of CD74 induces cell death of ALCL cells in various conditions, and an anti-CD74-directed antibody-drug conjugate efficiently kills ALCL cell lines. Furthermore, we reveal expression of the proto-oncogene and known CD74 interaction partner MET in a fraction of ALCL cases. These data give insights into ALCL pathogenesis and might help to develop new treatment strategies for ALCL. ABSTRACT: In 50–60% of cases, systemic anaplastic large cell lymphoma (ALCL) is characterized by the t(2;5)(p23;q35) or one of its variants, considered to be causative for anaplastic lymphoma kinase (ALK)-positive (ALK(+)) ALCL. Key pathogenic events in ALK-negative (ALK(−)) ALCL are less well defined. We have previously shown that deregulation of oncogenic genes surrounding the chromosomal breakpoints on 2p and 5q is a unifying feature of both ALK(+) and ALK(−) ALCL and predisposes for occurrence of t(2;5). Here, we report that the invariant chain of the MHC-II complex CD74 or li, which is encoded on 5q32, can act as signaling molecule, and whose expression in lymphoid cells is usually restricted to B cells, is aberrantly expressed in T cell-derived ALCL. Accordingly, ALCL shows an altered DNA methylation pattern of the CD74 locus compared to benign T cells. Functionally, CD74 ligation induces cell death of ALCL cells. Furthermore, CD74 engagement enhances the cytotoxic effects of conventional chemotherapeutics in ALCL cell lines, as well as the action of the ALK-inhibitor crizotinib in ALK(+) ALCL or of CD95 death-receptor signaling in ALK(−) ALCL. Additionally, a subset of ALCL cases expresses the proto-oncogene MET, which can form signaling complexes together with CD74. Finally, we demonstrate that the CD74-targeting antibody-drug conjugate STRO-001 efficiently and specifically kills CD74-positive ALCL cell lines in vitro. Taken together, these findings enabled us to demonstrate aberrant CD74-expression in ALCL cells, which might serve as tool for the development of new treatment strategies for this lymphoma entity
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