30 research outputs found
A non-energetic mechanism for glycine formation in the interstellar medium
The detection of the amino acid glycine and its amine precursor methylamine on the comet 67P/Churyumov-Gerasimenko by the Rosetta mission provides strong evidence for a cosmic origin of amino acids on Earth. How and when such molecules form along the process of star formation remains debated. Here we report the laboratory detection of glycine formed in the solid phase through atom and radical–radical addition surface reactions under dark interstellar cloud conditions. Our experiments, supported by astrochemical models, suggest that glycine forms without the need for ‘energetic’ irradiation (such as ultraviolet photons and cosmic rays) in interstellar water-rich ices, where it remains preserved, during a much earlier star-formation stage than previously assumed. We also confirm that solid methylamine is an important side-reaction product. A prestellar formation of glycine on ice grains provides the basis for a complex and ubiquitous prebiotic chemistry in space enriching the chemical content of planet-forming material
<i>C-elegans</i> model identifies genetic modifiers of alpha-synuclein inclusion formation during aging
Inclusions in the brain containing alpha-synuclein are the pathological hallmark of Parkinson's disease, but how these inclusions are formed and how this links to disease is poorly understood. We have developed a <i>C-elegans</i> model that makes it possible to monitor, in living animals, the formation of alpha-synuclein inclusions. In worms of old age, inclusions contain aggregated alpha-synuclein, resembling a critical pathological feature. We used genome-wide RNA interference to identify processes involved in inclusion formation, and identified 80 genes that, when knocked down, resulted in a premature increase in the number of inclusions. Quality control and vesicle-trafficking genes expressed in the ER/Golgi complex and vesicular compartments were overrepresented, indicating a specific role for these processes in alpha-synuclein inclusion formation. Suppressors include aging-associated genes, such as sir-2.1/SIRT1 and lagr-1/LASS2. Altogether, our data suggest a link between alpha-synuclein inclusion formation and cellular aging, likely through an endomembrane-related mechanism. The processes and genes identified here present a framework for further study of the disease mechanism and provide candidate susceptibility genes and drug targets for Parkinson's disease and other alpha-synuclein related disorders
An applied methodology for stakeholder identification in transdisciplinary research
In this paper we present a novel methodology for identifying stakeholders for the purpose of engaging with them in transdisciplinary, sustainability research projects. In transdisciplinary research, it is important to identify a range of stakeholders prior to the problem-focussed stages of research. Early engagement with diverse stakeholders creates space for them to influence the research process, including problem definition, from the start. However, current stakeholder analysis approaches ignore this initial identification process, or position it within the subsequent content-focussed stages of research. Our methodology was designed as part of a research project into a range of soil threats in seventeen case study locations throughout Europe. Our methodology was designed to be systematic across all sites. It is based on a snowball sampling approach that can be implemented by researchers with no prior experience of stakeholder research, and without requiring significant financial or time resources. It therefore fosters transdisciplinarity by empowering physical scientists to identify stakeholders and understand their roles. We describe the design process and outcomes, and consider their applicability to other research projects. Our methodology therefore consists of a two-phase process of design and implementation of an identification questionnaire. By explicitly including a design phase into the process, it is possible to tailor our methodology to other research projects
PIWI Associated siRNAs and piRNAs Specifically Require the Caenorhabditis elegans HEN1 Ortholog henn-1
Small RNAs—including piRNAs, miRNAs, and endogenous siRNAs—bind Argonaute proteins to form RNA silencing complexes that target coding genes, transposons, and aberrant RNAs. To assess the requirements for endogenous siRNA formation and activity in Caenorhabditis elegans, we developed a GFP-based sensor for the endogenous siRNA 22G siR-1, one of a set of abundant siRNAs processed from a precursor RNA mapping to the X chromosome, the X-cluster. Silencing of the sensor is also dependent on the partially complementary, unlinked 26G siR-O7 siRNA. We show that 26G siR-O7 acts in trans to initiate 22G siRNA formation from the X-cluster. The presence of several mispairs between 26G siR-O7 and the X-cluster mRNA, as well as mutagenesis of the siRNA sensor, indicates that siRNA target recognition is permissive to a degree of mispairing. From a candidate reverse genetic screen, we identified several factors required for 22G siR-1 activity, including the chromatin factors mes-4 and gfl-1, the Argonaute ergo-1, and the 3′ methyltransferase henn-1. Quantitative RT–PCR of small RNAs in a henn-1 mutant and deep sequencing of methylated small RNAs indicate that siRNAs and piRNAs that associate with PIWI clade Argonautes are methylated by HENN-1, while siRNAs and miRNAs that associate with non-PIWI clade Argonautes are not. Thus, PIWI-class Argonaute proteins are specifically adapted to associate with methylated small RNAs in C. elegans
IRFEL Selective Irradiation of Amorphous Solid Water: from Dangling to Bulk Modes
Amorphous solid water (ASW) is one of the most widely studied solid phase
systems. A better understanding of the nature of inter- and intramolecular
forces in ASW is, however, still required to correctly interpret the catalytic
role of ASW in the formation and preservation of molecular species in
environments such as the icy surfaces of Solar System objects, on interstellar
icy dust grains and potentially even in the upper layers of the Earth's
atmosphere. In this work, we have systematically exposed porous ASW (pASW) to
mid-infrared radiation generated by a free-electron laser at the HFML-FELIX
facility in the Netherlands to study the effect of vibrational energy injection
into the surface and bulk modes of pASW. During multiple sequential
irradiations on the same ice spot, we observed selective effects both at the
surface and in the bulk of the ice. Although the density of states in pASW
should allow for a fast vibrational relaxation through the H-bonded network,
part of the injected energy is converted into structural ice changes as
illustrated by the observation of spectral modifications when performing
Fourier transform infrared spectroscopy in reflection-absorption mode. Future
studies will include the quantification of such effects by systematically
investigating ice thickness, ice morphology, and ice composition.Comment: Published in The Journal of Physical Chemistry
Infrared Resonant Vibrationally Induced Restructuring of Amorphous Solid Water
Amorphous solid water (ASW) is abundantly present in the interstellar medium,
where it forms a mantle on interstellar dust particles and it is the precursor
for cometary ices. In space, ASW acts as substrate for interstellar surface
chemistry leading to complex molecules and it is postulated to play a critical
role in proton-transfer reactions. Although ASW is widely studied and is
generally well characterized by different techniques, energetically-induced
structural changes, such as ion, electron and photon irradiation, in these
materials are less well understood. Selective pumping of specific infrared (IR)
vibrational modes can aid in understanding the role of vibrations in
restructuring of hydrogen bonding networks. Here we present the first
experimental results on hydrogen bonding changes in ASW induced by the intense,
nearly monochromatic mid-IR free-electron laser (FEL) radiation of the FELIX-2
beamline at the FELIX Laboratory at the Radboud University in Nijmegen, the
Netherlands. The changes are monitored by reflection-absorption infrared
spectroscopy. Upon resonant irradiation, a modification in IR absorption band
profile of ASW is observed in agreement with a growing crystalline-like
contribution and a decreasing amorphous contribution. This phenomenon saturates
within a few minutes of FEL irradiation, modifying upwards of 94~\% of the
irradiated ice. The effect is further analysed in terms of hydrogen bonding
donors and acceptors and the experiments are complimented with Molecular
Dynamics simulations to constrain the effect at the molecular level.Comment: Accepted for publication in J. Phys. Chem.
Infrared free-electron laser irradiation of carbon dioxide ice
Interstellar ice grains are believed to play a key role in the formation of many of the simple and complex organic species detected in space. However, many fundamental questions on the physicochemical processes linked to the formation and survival of species in ice grains remain unanswered. Field work at large-scale facilities such as free-electron lasers (FELs) can aid the investigation of the composition and morphology of ice grains by providing novel tools to the laboratory astrophysics community. We combined the high tunability, wide infrared spectral range and intensity of the FEL beam line FELIX-2 at the HFML-FELIX Laboratory in The Netherlands with the characteristics of the ultrahigh vacuum LISA end station to perform wavelength-dependent mid-IR irradiation experiments of space-relevant pure carbon dioxide (CO2) ice at 20 K. We used the intense monochromatic radiation of FELIX to inject vibrational energy at selected frequencies into the CO2 ice to study ice restructuring effects in situ by Fourier Transform Reflection–Absorption Infrared (FT-RAIR) spectroscopy. This work improves our understanding of how vibrational energy introduced by external triggers such as photons, electrons, cosmic rays, and thermal heating coming from a nascent protostar or field stars is dissipated in an interstellar icy dust grain in space. Moreover, it adds to the current literature debate concerning the amorphous and polycrystalline structure of CO2 ice observed upon deposition at low temperatures, showing that, under our experimental conditions, CO2 ice presents amorphous characteristics when deposited at 20 K and is unambiguously crystalline if deposited at 75 K
Surface formation routes of interstellar molecules: Hydrogenation reactions in simple ices
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Predicting clinical benefit from everolimus in patients with advanced solid tumors, the CPCT-03 study
Differential Impact of the HEN1 Homolog HENN-1 on 21U and 26G RNAs in the Germline of Caenorhabditis elegans
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