805 research outputs found
Disease-associated mutations within the yeast DNAJB6 homolog Sis1 slow conformer-specific substrate processing and can be corrected by the modulation of nucleotide exchange factors
Molecular chaperones, or heat shock proteins (HSPs), protect against the toxic misfolding and aggregation of proteins. As such, mutations or deficiencies within the chaperone network can lead to disease. Dominant mutations within DNAJB6 (Hsp40)-an Hsp70 co-chaperone-lead to a protein aggregation-linked myopathy termed Limb-Girdle Muscular Dystrophy Type D1 (LGMDD1). Here, we used the yeast prion model client in conjunction with in vitro chaperone activity assays to gain mechanistic insights into the molecular basis of LGMDD1. Here, we show how mutations analogous to those found in LGMDD1 affect Sis1 (a functional homolog of human DNAJB6) function by altering the structure of client protein aggregates, interfering with the Hsp70 ATPase cycle, dimerization and substrate processing; poisoning the function of wild-type protein. These results uncover the mechanisms through which LGMDD1-associated mutations alter chaperone activity, and provide insights relevant to potential therapeutic interventions
Search for Gravitational Waves from Scorpius X-1 in LIGO O3 Data With Corrected Orbital Ephemeris
Improved observational constraints on the orbital parameters of the low-mass
X-ray binary Scorpius~X-1 were recently published in Killestein et al (2023).
In the process, errors were corrected in previous orbital ephemerides, which
have been used in searches for continuous gravitational waves from Sco~X-1
using data from the Advanced LIGO detectors. We present the results of a
re-analysis of LIGO detector data from the third observing run of Advanced LIGO
and Advanced Virgo using a model-based cross-correlation search. The corrected
region of parameter space, which was not covered by previous searches, was
about 1/3 as large as the region searched in the original O3 analysis, reducing
the required computing time. We have confirmed that no detectable signal is
present over a range of gravitational-wave frequencies from to
, analogous to the null result of Abbott et al (2022). Our
search sensitivity is comparable to that of Abbott et al (2022), who set upper
limits corresponding, between and , to an
amplitude of about when marginalized isotropically over the
unknown inclination angle of the neutron star's rotation axis, or less than
assuming the optimal orientation.Comment: 8 pages, 3 figures, 2 tables. Typeset with AASTeX 6.3.1. Accepted for
publication in The Astrophysical Journal. arXiv admin note: text overlap with
arXiv:2209.0286
Genetic Analysis Workshop 16: Strategies for genome-wide association study analyses
National Institutes of Health (AR44422, N01-AR-7-2232); Genome Canada and Associations AFP; Polyarctique-Groupe Taitbout; Rhumatisme et Travail; Arthritis Research Campaign; National Institute of General Medical Sciences (R01 GM31575
Whitefish Wars: Pangasius, politics and consumer confusion in Europe
Rapid growth in production of the farmed Vietnamese whitefish pangasius and its trade with the European Union has provoked criticism of the fish’s environmental, social and safety credentials by actors including WWF and Members of the European Parliament and associated negative media coverage. This paper reviews the range of claims communicated about pangasius (identified as a form of mass mediated risk governance), in light of scientific evidence and analysis of data from the EU’s Rapid Alert System for Food and Feeds food safety notification system for imported seafood. This analysis shows pangasius is to be generally safe, environmentally benign, and beneficial for actors along the international value chains that characterise the trade. The case is made that increasingly politicised debates in Europe around risk and uncertainty are potentially counterproductive for EU seafood security and European aquaculture industry, and that the trade in pangasius can contribute to sustainable seafood consumption in a number of ways. Transparent evidence-based assessment and systems for communicating complex issues of risk for products such as pangasius are required in order to support continuance of fair and mutually beneficial trade
Publisher Correction:Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals (Nature Genetics, (2020), 52, 12, (1314-1332), 10.1038/s41588-020-00713-x)
In the version of this article originally published, the e-mail address of corresponding author Patricia B. Munroe was incorrect. The error has been corrected in the HTML and PDF versions of the article
Gravitational Waves From Known Pulsars: Results From The Initial Detector Era
We present the results of searches for gravitational waves from a large selection of pulsars using data from the most recent science runs (S6, VSR2 and VSR4) of the initial generation of interferometric gravitational wave detectors LIGO (Laser Interferometric Gravitational-wave Observatory) and Virgo. We do not see evidence for gravitational wave emission from any of the targeted sources but produce upper limits on the emission amplitude. We highlight the results from seven young pulsars with large spin-down luminosities. We reach within a factor of five of the canonical spin-down limit for all seven of these, whilst for the Crab and Vela pulsars we further surpass their spin-down limits. We present new or updated limits for 172 other pulsars (including both young and millisecond pulsars). Now that the detectors are undergoing major upgrades, and, for completeness, we bring together all of the most up-to-date results from all pulsars searched for during the operations of the first-generation LIGO, Virgo and GEO600 detectors. This gives a total of 195 pulsars including the most recent results described in this paper.United States National Science FoundationScience and Technology Facilities Council of the United KingdomMax-Planck-SocietyState of Niedersachsen/GermanyAustralian Research CouncilInternational Science Linkages program of the Commonwealth of AustraliaCouncil of Scientific and Industrial Research of IndiaIstituto Nazionale di Fisica Nucleare of ItalySpanish Ministerio de Economia y CompetitividadConselleria d'Economia Hisenda i Innovacio of the Govern de les Illes BalearsNetherlands Organisation for Scientific ResearchPolish Ministry of Science and Higher EducationFOCUS Programme of Foundation for Polish ScienceRoyal SocietyScottish Funding CouncilScottish Universities Physics AllianceNational Aeronautics and Space AdministrationOTKA of HungaryLyon Institute of Origins (LIO)National Research Foundation of KoreaIndustry CanadaProvince of Ontario through the Ministry of Economic Development and InnovationNational Science and Engineering Research Council CanadaCarnegie TrustLeverhulme TrustDavid and Lucile Packard FoundationResearch CorporationAlfred P. Sloan FoundationAstronom
Search for gravitational waves associated with the InterPlanetary Network short gamma ray bursts
We outline the scientific motivation behind a search for gravitational waves
associated with short gamma ray bursts detected by the InterPlanetary Network
(IPN) during LIGO's fifth science run and Virgo's first science run. The IPN
localisation of short gamma ray bursts is limited to extended error boxes of
different shapes and sizes and a search on these error boxes poses a series of
challenges for data analysis. We will discuss these challenges and outline the
methods to optimise the search over these error boxes.Comment: Methods paper; Proceedings for Eduardo Amaldi 9 Conference on
Gravitational Waves, July 2011, Cardiff, U
Swift follow-up observations of candidate gravitational-wave transient events
We present the first multi-wavelength follow-up observations of two candidate
gravitational-wave (GW) transient events recorded by LIGO and Virgo in their
2009-2010 science run. The events were selected with low latency by the network
of GW detectors and their candidate sky locations were observed by the Swift
observatory. Image transient detection was used to analyze the collected
electromagnetic data, which were found to be consistent with background.
Off-line analysis of the GW data alone has also established that the selected
GW events show no evidence of an astrophysical origin; one of them is
consistent with background and the other one was a test, part of a "blind
injection challenge". With this work we demonstrate the feasibility of rapid
follow-ups of GW transients and establish the sensitivity improvement joint
electromagnetic and GW observations could bring. This is a first step toward an
electromagnetic follow-up program in the regime of routine detections with the
advanced GW instruments expected within this decade. In that regime
multi-wavelength observations will play a significant role in completing the
astrophysical identification of GW sources. We present the methods and results
from this first combined analysis and discuss its implications in terms of
sensitivity for the present and future instruments.Comment: Submitted for publication 2012 May 25, accepted 2012 October 25,
published 2012 November 21, in ApJS, 203, 28 (
http://stacks.iop.org/0067-0049/203/28 ); 14 pages, 3 figures, 6 tables;
LIGO-P1100038; Science summary at
http://www.ligo.org/science/Publication-S6LVSwift/index.php ; Public access
area to figures, tables at
https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=p110003
A First Search for coincident Gravitational Waves and High Energy Neutrinos using LIGO, Virgo and ANTARES data from 2007
We present the results of the first search for gravitational wave bursts
associated with high energy neutrinos. Together, these messengers could reveal
new, hidden sources that are not observed by conventional photon astronomy,
particularly at high energy. Our search uses neutrinos detected by the
underwater neutrino telescope ANTARES in its 5 line configuration during the
period January - September 2007, which coincided with the fifth and first
science runs of LIGO and Virgo, respectively. The LIGO-Virgo data were analysed
for candidate gravitational-wave signals coincident in time and direction with
the neutrino events. No significant coincident events were observed. We place
limits on the density of joint high energy neutrino - gravitational wave
emission events in the local universe, and compare them with densities of
merger and core-collapse events.Comment: 19 pages, 8 figures, science summary page at
http://www.ligo.org/science/Publication-S5LV_ANTARES/index.php. Public access
area to figures, tables at
https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=p120000
First Low-Latency LIGO+Virgo Search for Binary Inspirals and their Electromagnetic Counterparts
Aims. The detection and measurement of gravitational-waves from coalescing
neutron-star binary systems is an important science goal for ground-based
gravitational-wave detectors. In addition to emitting gravitational-waves at
frequencies that span the most sensitive bands of the LIGO and Virgo detectors,
these sources are also amongst the most likely to produce an electromagnetic
counterpart to the gravitational-wave emission. A joint detection of the
gravitational-wave and electromagnetic signals would provide a powerful new
probe for astronomy.
Methods. During the period between September 19 and October 20, 2010, the
first low-latency search for gravitational-waves from binary inspirals in LIGO
and Virgo data was conducted. The resulting triggers were sent to
electromagnetic observatories for followup. We describe the generation and
processing of the low-latency gravitational-wave triggers. The results of the
electromagnetic image analysis will be described elsewhere.
Results. Over the course of the science run, three gravitational-wave
triggers passed all of the low-latency selection cuts. Of these, one was
followed up by several of our observational partners. Analysis of the
gravitational-wave data leads to an estimated false alarm rate of once every
6.4 days, falling far short of the requirement for a detection based solely on
gravitational-wave data.Comment: 13 pages, 13 figures. For a repository of data used in the
publication, go to:
http://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=P1100065 Also see the
announcement for this paper on ligo.org at:
http://www.ligo.org/science/Publication-S6CBCLowLatency
- âŠ