2,540 research outputs found
Trypanosoma brucei PRMT1 Is a Nucleic Acid Binding Protein with a Role in Energy Metabolism and the Starvation Stress Response.
In Trypanosoma brucei and related kinetoplastid parasites, transcription of protein coding genes is largely unregulated. Rather, mRNA binding proteins, which impact processes such as transcript stability and translation efficiency, are the predominant regulators of gene expression. Arginine methylation is a posttranslational modification that preferentially targets RNA binding proteins and is, therefore, likely to have a substantial impact on T. brucei biology. The data presented here demonstrate that cells depleted of T. brucei PRMT1 (TbPRMT1), a major type I protein arginine methyltransferase, exhibit decreased virulence in an animal model. To understand the basis of this phenotype, quantitative global proteomics was employed to measure protein steady-state levels in cells lacking TbPRMT1. The approach revealed striking changes in proteins involved in energy metabolism. Most prominent were a decrease in glycolytic enzyme abundance and an increase in proline degradation pathway components, changes that resemble the metabolic remodeling that occurs during T. brucei life cycle progression. The work describes several RNA binding proteins whose association with mRNA was altered in TbPRMT1-depleted cells, and a large number of TbPRMT1-interacting proteins, thereby highlighting potential TbPRMT1 substrates. Many proteins involved in the T. brucei starvation stress response were found to interact with TbPRMT1, prompting analysis of the response of TbPRMT1-depleted cells to nutrient deprivation. Indeed, depletion of TbPRMT1 strongly hinders the ability of T. brucei to form cytoplasmic mRNA granules under starvation conditions. Finally, this work shows that TbPRMT1 itself binds nucleic acids in vitro and in vivo, a feature completely novel to protein arginine methyltransferases.IMPORTANCETrypanosoma brucei infection causes human African trypanosomiasis, also known as sleeping sickness, a disease with a nearly 100% fatality rate when untreated. Current drugs are expensive, toxic, and highly impractical to administer, prompting the community to explore various unique aspects of T. brucei biology in search of better treatments. In this study, we identified the protein arginine methyltransferase (PRMT), TbPRMT1, as a factor that modulates numerous aspects of T. brucei biology. These include glycolysis and life cycle progression signaling, both of which are being intensely researched toward identification of potential drug targets. Our data will aid research in those fields. Furthermore, we demonstrate for the first time a direct association of a PRMT with nucleic acids, a finding we believe could translate to other organisms, including humans, thereby impacting research in fields as distant as human cancer biology and immune response modulation. Copyright Ā© 2018 KafkovĆ” et al
Orion Optical Navigation Performance and Testing
The Orion Optical Navigation System, which is designed to perform the navigation which will allow the crew to return safely to Earth in the event of a permanent loss of communications with the ground, has been matured through analysis and testing. This paper will detail the extensive tests and analysis that have gone into fleshing out the performance of the system in the face of numerous constraints placed on the optical navigation system
Combination of herbivore removal and nitrogen deposition increases upland carbon storage
Ā© 2015 The Authors. Global Change Biology Published by John Wiley & Sons Ltd. Acknowledgements We thank Ruth Mitchell, Alison Hester, Bob Mardon, Eoghain Maclean, David Welch, National Trust for Scotland, Scottish Natural Heritage and the Woodland Trust for helping find appropriate exclosures and granting access permission. We thank Nick Littlewood and Antonio Lopez Nogueira for their assistance in the field and processing samples in the lab and Ron Smith and Tony Dore for providing N deposition data. SWS was funded by a BBSRC studentship.Non peer reviewedPublisher PD
Distributed algorithms for self-disassembly in modular robots
Thesis (M. Eng. and S.B.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2006.Includes bibliographical references (p. 225-226).We developed a modular robotic system that behaves as programmable matter. Specifically, we designed, implemented, and tested a collection of robots that, starting from an amorphous arrangement, can be assembled into arbitrary shapes and then commanded to self-disassemble in an organized manner. The 28 modules in the system were implemented as 1.77-inch autonomous cubes that were able to connect to and communicate with their immediate neighbors. Two cooperating microprocessors controlled the modules' magnetic connection mechanisms and infrared communication interfaces. We developed algorithms for the distributed communication and control of the system which allowed the modules to perform localization and distribute shape information in an efficient manner. When assembled into a structure, the modules formed a system which could be virtually sculpted using a computer interface which we also designed. By employing the sculpting process, we were able to accurately control the final shape assumed by the structure. Unnecessary modules disconnected from the structure and fell away. The results of close to 200 experiments showed the that the algorithms operated as expected and were able to successfully control the distributed system. We were able to quickly form one, two, and three dimensional structures.by Kyle W. Gilpin.M.Eng.and S.B
Demonstrating high-precision photometry with a CubeSat: ASTERIA observations of 55 Cancri e
ASTERIA (Arcsecond Space Telescope Enabling Research In Astrophysics) is a 6U
CubeSat space telescope (10 cm x 20 cm x 30 cm, 10 kg). ASTERIA's primary
mission objective was demonstrating two key technologies for reducing
systematic noise in photometric observations: high-precision pointing control
and high-stabilty thermal control. ASTERIA demonstrated 0.5 arcsecond RMS
pointing stability and 10 milliKelvin thermal control of its camera
payload during its primary mission, a significant improvement in pointing and
thermal performance compared to other spacecraft in ASTERIA's size and mass
class. ASTERIA launched in August 2017 and deployed from the International
Space Station (ISS) November 2017. During the prime mission (November 2017 --
February 2018) and the first extended mission that followed (March 2018 - May
2018), ASTERIA conducted opportunistic science observations which included
collection of photometric data on 55 Cancri, a nearby exoplanetary system with
a super-Earth transiting planet. The 55 Cancri data were reduced using a custom
pipeline to correct CMOS detector column-dependent gain variations. A Markov
Chain Monte Carlo (MCMC) approach was used to simultaneously detrend the
photometry using a simple baseline model and fit a transit model. ASTERIA made
a marginal detection of the known transiting exoplanet 55 Cancri e
(~\Rearth), measuring a transit depth of ppm. This is the
first detection of an exoplanet transit by a CubeSat. The successful detection
of super-Earth 55 Cancri e demonstrates that small, inexpensive spacecraft can
deliver high-precision photometric measurements.Comment: 23 pages, 9 figures. Accepted in A
Alkenones as a promising green alternative for waxes in cosmetics and personal care products
Ā© The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Cosmetics 5 (2018): 34, doi:10.3390/cosmetics5020034.The move toward green, sustainable, natural products has been growing in the cosmetic and personal care industry. Ingredients derived from marine organisms and algae are present in many cosmetic products. In this study, a new green ingredient, a wax (i.e., long-chain alkenones) derived from Isochyrsis sp., was evaluated as an alternative for cosmetic waxes. First, the melting point was determined (71.1ā77.4 Ā°C), then the alkenonesā thickening capability in five emollients was evaluated and compared to microcrystalline wax and ozokerite. Alkenones were compatible with three emollients and thickened the emollients similarly to the other waxes. Then, lipsticks and lip balms were formulated with and without alkenones. All products remained stable at room temperature for 10 weeks. Lipstick formulated with alkenones was the most resistant to high temperature. Finally, alkenones were compared to three cosmetic thickening waxes in creams. Viscosity, rheology, and stability of the creams were evaluated. All creams had a gel-like behavior. Both viscosity and storage modulus increased in the same order: cream with alkenones < cetyl alcohol < stearic acid < glyceryl monostearate. Overall, alkenonesā performance was comparable to the other three waxes. Alkenones can thus offer a potential green choice as a new cosmetic structuring agent.This research was funded by the Washington Research Foundation and a private donor from friends of
the Woods Hole Oceanographic Institution, grant number N-126478
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Allele-specific NKX2-5 binding underlies multiple genetic associations with human electrocardiographic traits.
The cardiac transcription factor (TF) gene NKX2-5 has been associated with electrocardiographic (EKG) traits through genome-wide association studies (GWASs), but the extent to which differential binding of NKX2-5 at common regulatory variants contributes to these traits has not yet been studied. We analyzed transcriptomic and epigenomic data from induced pluripotent stem cell-derived cardiomyocytes from seven related individuals, and identified ~2,000 single-nucleotide variants associated with allele-specific effects (ASE-SNVs) on NKX2-5 binding. NKX2-5 ASE-SNVs were enriched for altered TF motifs, for heart-specific expression quantitative trait loci and for EKG GWAS signals. Using fine-mapping combined with epigenomic data from induced pluripotent stem cell-derived cardiomyocytes, we prioritized candidate causal variants for EKG traits, many of which were NKX2-5 ASE-SNVs. Experimentally characterizing two NKX2-5 ASE-SNVs (rs3807989 and rs590041) showed that they modulate the expression of target genes via differential protein binding in cardiac cells, indicating that they are functional variants underlying EKG GWAS signals. Our results show that differential NKX2-5 binding at numerous regulatory variants across the genome contributes to EKG phenotypes
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