1,109 research outputs found
The long noncoding RNA neuroLNC regulates presynaptic activity by interacting with the neurodegeneration-associated protein TDP-43
The cellular and the molecular mechanisms by which long noncoding RNAs (lncRNAs) may regulate presynaptic function and neuronal activity are largely unexplored. Here, we established an integrated screening strategy to discover lncRNAs implicated in neurotransmitter and synaptic vesicle release. With this approach, we identified neuroLNC, a neuron-specific nuclear lncRNA conserved from rodents to humans. NeuroLNC is tuned by synaptic activity and influences several other essential aspects of neuronal development including calcium influx, neuritogenesis, and neuronal migration in vivo. We defined the molecular interactors of neuroLNC in detail using chromatin isolation by RNA purification, RNA interactome analysis, and protein mass spectrometry. We found that the effects of neuroLNC on synaptic vesicle release require interaction with the RNA-binding protein TDP-43 (TAR DNA binding protein-43) and the selective stabilization of mRNAs encoding for presynaptic proteins. These results provide the first proof of an lncRNA that orchestrates neuronal excitability by influencing presynaptic function
Brief training in mindfulness may normalize a blunted error-related negativity in chronically depressed patients
This is the final version of the article. Available from the publisher via the DOI in this record.The error-related negativity (ERN), an evoked-potential that arises in response to the commission of errors, is an important early indicator of self-regulatory capacities. In this study we investigated whether brief mindfulness training can reverse ERN deficits in chronically depressed patients. The ERN was assessed in a sustained attention task. Chronically depressed patients (n = 59) showed significantly blunted expression of the ERN in frontocentral and frontal regions, relative to healthy controls (n = 18). Following two weeks of training, the patients (n = 24) in the mindfulness condition showed a significantly increased ERN magnitude in the frontal region, but there were no significant changes in patients who had received a resting control (n = 22). The findings suggest that brief training in mindfulness may help normalize aberrations in the ERN in chronically depressed patients, providing preliminary evidence for the responsiveness of this parameter to mental training.This research
was funded by German Research Foundation Grant No.
BA2255 3-1, awarded to T.B. T.B. was also supported by a
Heisenberg Fellowship from the German Research
Foundation (BA2255 2-1
Arsenic metabolism in high altitude modern stromatolites revealed by metagenomic analysis
Modern stromatolites thrive only in selected locations in the world. Socompa Lake, located in the Andean plateau at 3570 masl, is one of the numerous extreme Andean microbial ecosystems described over recent years. Extreme environmental conditions include hypersalinity, high UV incidence, and high arsenic content, among others. After Socompa’s stromatolite microbial communities were analysed by metagenomic DNA sequencing, taxonomic classification showed dominance of Proteobacteria, Bacteroidetes and Firmicutes, and a remarkably high number of unclassified sequences. A functional analysis indicated that carbon fixation might occur not only by the Calvin-Benson cycle, but also through alternative pathways such as the reverse TCA cycle, and the reductive acetyl-CoA pathway. Deltaproteobacteria were involved both in sulfate reduction and nitrogen fixation. Significant differences were found when comparing the Socompa stromatolite metagenome to the Shark Bay (Australia) smooth mat metagenome: namely, those involving stress related processes, particularly, arsenic resistance. An in-depth analysis revealed a surprisingly diverse metabolism comprising all known types of As resistance and energy generating pathways. While the ars operon was the main mechanism, an important abundance of arsM genes was observed in selected phyla. The data resulting from this work will prove a cornerstone for further studies on this rare microbial community.EEA RafaelaFil: Kurth, Daniel German. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Planta Piloto de Procesos Industriales Microbiológicos; ArgentinaFil: Amadio, Ariel F. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Rafaela; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ordoñez, Omar F. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Planta Piloto de Procesos Industriales Microbiológicos; ArgentinaFil: Allbarracín, Virginia H. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Planta Piloto de Procesos Industriales Microbiológicos; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales. Instituto Miguel Lillo; ArgentinaFil: Farías, María E. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Planta Piloto de Procesos Industriales Microbiológicos; ArgentinaFil: Gärtner, Wolfgang. Max-Planck Institute for Chemical Energy Conversion; Alemani
Fingerprints of carbon defects in vibrational spectra of gallium nitride (GaN) consider-ing the isotope effect
This work examines the carbon defects associated with recently reported and
novel peaks of infrared (IR) absorption and Raman scattering appearing in GaN
crystals at carbon () doping in the range of concentrations from
to . 14 unique vibrational modes of defects
are observed in GaN samples grown by hydride vapor phase epitaxy (HVPE) and
then compared with defect properties predicted from first-principles
calculations. The vibrational frequency shift in two enriched samples
related to the effect of the isotope mass indicates six distinct configurations
of the carbon-containing point defects. The effect of the isotope replacement
is well reproduced by the density functional theory (DFT) calculations.
Specific attention is paid to the most pronounced defects, namely tri-carbon
complexes() and carbon substituting for nitrogen . The position
of the transition level (+/0) in the bandgap found for defects by
DFT at 1.1 eV above the valence band maximum, suggest that
provides compensation of . defects are observed to be
prominent, yet have high formation energies in DFT calculations. Regarding
defects, it is shown that the host Ga and N atoms are involved in the
defect's delocalized vibrations and significantly affect the isotopic frequency
shift. Much more faint vibrational modes are found from di-atomic carbon-carbon
and carbon-hydrogen (C-H) complexes. Also, we note changes of vibrational mode
intensities of , , C-H, and defects in the IR
absorption spectra upon irradiation in the defect-related UV/visible absorption
range. Finally, it is demonstrated that the resonant enhancement of the Raman
process in the range of defect absorption above 2.5 eV enables the detection of
defects at carbon doping concentrations as low as
How was it for you? Experiences of participatory design in the UK health service
Improving co-design methods implies that we need to understand those methods, paying attention to not only the effect of method choices on design outcomes, but also how methods affect the people involved in co-design. In this article, we explore participants' experiences from a year-long participatory health service design project to develop ‘Better Outpatient Services for Older People’. The project followed a defined method called experience-based design (EBD), which represented the state of the art in participatory service design within the UK National Health Service. A sample of participants in the project took part in semi-structured interviews reflecting on their involvement in and their feelings about the project. Our findings suggest that the EBD method that we employed was successful in establishing positive working relationships among the different groups of stakeholders (staff, patients, carers, advocates and design researchers), although conflicts remained throughout the project. Participants' experiences highlighted issues of wider relevance in such participatory design: cost versus benefit, sense of project momentum, locus of control, and assumptions about how change takes place in a complex environment. We propose tactics for dealing with these issues that inform the future development of techniques in user-centred healthcare design
Evolutionary trajectories in rugged fitness landscapes
We consider the evolutionary trajectories traced out by an infinite
population undergoing mutation-selection dynamics in static, uncorrelated
random fitness landscapes. Starting from the population that consists of a
single genotype, the most populated genotype \textit{jumps} from a local
fitness maximum to another and eventually reaches the global maximum. We use a
strong selection limit, which reduces the dynamics beyond the first time step
to the competition between independent mutant subpopulations, to study the
dynamics of this model and of a simpler one-dimensional model which ignores the
geometry of the sequence space. We find that the fit genotypes that appear
along a trajectory are a subset of suitably defined fitness \textit{records},
and exploit several results from the record theory for non-identically
distributed random variables. The genotypes that contribute to the trajectory
are those records that are not \textit{bypassed} by superior records arising
further away from the initial population. Several conjectures concerning the
statistics of bypassing are extracted from numerical simulations. In
particular, for the one-dimensional model, we propose a simple relation between
the bypassing probability and the dynamic exponent which describes the scaling
of the typical evolution time with genome size. The latter can be determined
exactly in terms of the extremal properties of the fitness distribution.Comment: Figures in color; minor revisions in tex
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