245 research outputs found

    Alternative splicing coupled mRNA decay shapes the temperature‐dependent transcriptome

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    Mammalian body temperature oscillates with the time of the dayand is altered in diverse pathological conditions. We recently iden-tified a body temperature-sensitive thermometer-like kinase,which alters SR protein phosphorylation and thereby globallycontrols alternative splicing (AS). AS can generate unproductivevariants which are recognized and degraded by diverse mRNAdecay pathways—including nonsense-mediated decay (NMD). Herewe show extensive coupling of body temperature-controlled AS tomRNA decay, leading to global control of temperature-dependentgene expression (GE). Temperature-controlled, decay-inducingsplicing events are evolutionarily conserved and pervasively foundwithin RNA-binding proteins, including most SR proteins. AS-coupledpoison exon inclusion is essential for rhythmic GE of SR proteins andhas a global role in establishing temperature-dependent rhythmicGE profiles, both in mammals under circadian body temperaturecycles and in plants in response to ambient temperature changes.Together, these data identify body temperature-driven AS-coupledmRNA decay as an evolutionary ancient, core clock-independentmechanism to generate rhythmic GE

    Strengthening regulatory science in academia:STARS, an EU initiative to bridge the translational gap

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    Truly disruptive medicine innovation and new treatment paradigms tend to start in non-commercial research institutions. However, the lack of mutual understanding between medicine developers and regulators when it comes to medicine development significantly delays or even prevents the access of patients to these innovations. Here, we outline what regulatory-related barriers hamper the translational development of novel products or new treatment paradigms initiated in academia, and propose key steps towards improved regulatory dialogue among academia, funding bodies and regulatory authorities. Moreover, we briefly describe how the STARS (Strengthening Training of Academia in Regulatory Science) project aims to reach out to medicine innovators in academia to bridge the regulatory knowledge gap and enhance this dialogue to facilitate the implementation of academic research findings in clinical practice

    Proposing a Governance model for environmental crises

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    During August 2021, a wildfire outbreak in Evia, Greece's second largest island, resulted in a major environmental and economic crisis. Apart from biodiversity and habitat loss, the disaster triggered a financial crisis because it wiped out wood-productive forests and outdoor areas that attract visitors. This crisis highlighted the need for a new governance model in order to respond to environmental crises more effectively. The aim of this study was to investigate the acceptance and attitudes of relevant stakeholders towards establishing a Hub a proposed governance model responsible for monitoring and restoring the natural capital and biodiversity after environmental crises. Results based on quantitative data collected via questionnaires showed that most respondents were positive to the Hub and perceived that its main functions should be to recommend measures after environmental crises and to facilitate cooperation among involved stakeholders. Moreover, results pointed to preferred funding sources, stakeholder groups that should participate in the Hub and key performance indicators (KPIs) for monitoring Hub's performance. The applied methodology could guide the establishment of governance models both in the study area and other countries facing environmental crises

    Propylene Carbonate Reexamined: Mode-Coupling ÎČ\beta Scaling without Factorisation ?

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    The dynamic susceptibility of propylene carbonate in the moderately viscous regime above TcT_{\rm c} is reinvestigated by incoherent neutron and depolarised light scattering, and compared to dielectric loss and solvation response. Depending on the strength of α\alpha relaxation, a more or less extended ÎČ\beta scaling regime is found. Mode-coupling fits yield consistently λ=0.72\lambda=0.72 and Tc=182T_{\rm c}=182 K, although different positions of the susceptibility minimum indicate that not all observables have reached the universal asymptotics

    Electrical properties of InSb quantum wells remotely doped with Si

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    Two-dimensional electron systems were realized in InSb quantum wells with Al x In 1ÏȘx Sb barrier layers ␊-doped with Si. Measured electron mobilities in multiple-quantum-well structures were as high as 41 000 cm 2 /V s at room temperature and 209 000 cm 2 /V s at 77 K. Simple models can be used to explain the observed dependencies of the electron density on the quantum-well-to-dopant distance and on the number of quantum wells. Characterization by atomic force microscopy indicates that layer morphology may be a factor limiting electron mobility

    Comparison of air fluorescence and ionization measurements of E.M. shower depth profiles: test of a UHECR detector technique

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    Measurements are reported on the fluorescence of air as a function of depth in electromagnetic showers initiated by bunches of 28.5 GeV electrons. The light yield is compared with the expected and observed depth profiles of ionization in the showers. It validates the use of atmospheric fluorescence profiles in measuring ultra high energy cosmic rays.Comment: 22 pages, 11 figures. Submitted to Astroparticle Physic

    Long-term carbon sink in Borneo's forests halted by drought and vulnerable to edge effects

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    Less than half of anthropogenic carbon dioxide emissions remain in the atmosphere. While carbon balance models imply large carbon uptake in tropical forests, direct on-the-ground observations are still lacking in Southeast Asia. Here, using long-term plot monitoring records of up to half a century, we find that intact forests in Borneo gained 0.43 Mg C ha‟Âč per year (95% CI 0.14—0.72, mean period 1988-2010) above-ground live biomass. These results closely match those from African and Amazonian plot networks, suggesting that the world's remaining intact tropical forests are now en masse out-of-equilibrium. Although both pan-tropical and long-term, the sink in remaining intact forests appears vulnerable to climate and land use changes. Across Borneo the 1997-1998 El Niño drought temporarily halted the carbon sink by increasing tree mortality, while fragmentation persistently offset the sink and turned many edge-affected forests into a carbon source to the atmosphere
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