184 research outputs found
Exploring three correlates of thought suppression: attention, absorbtion, and cognitive load
Previous studies evaluating the probability of successful thought suppression (attempts to rid our minds of repeated unwanted thoughts) have relied solely upon internal mental distracters (Wegner, 1989), characterizing thought suppression to be a controlled rather than an automatic process. As an alternative approach, the effects of attention actively focused on limited external stimuli were studied in order to achieve easy, effortless, and successful thought suppression. Participants included students enrolled in undergraduate psychology courses. Experiment 1 showed that the presence of cognitive load (computerized tests of perceptual skills) occupied conscious capacity sufficiently so that attempts to suppress both mundane (tree) and exciting (sex) target thoughts were successful. Experiment 2 revealed that the physiological effects of exciting thoughts (measured via electrodermal activity) were higher for participants who were rated as having a predisposition toward successful suppression, although contrary to the results of Experiment 1, cognitive load did not have any effect on suppression or expression of target thoughts. Experiment 3 found that the type of cognitive load (motoric or attentional) was a factor in achieving successful thought suppression. Collectively, these findings suggest that experience seems to be a more effective thought distracter relative to traditional internal mental distracters, but only when attention is captured involuntarily and by an appropriately challenging level of cognitive load
Scientists' Warning to Humanity on Threats to Indigenous and Local Knowledge Systems
The knowledge systems and practices of Indigenous Peoples and local communities play critical roles in safeguarding the biological and cultural diversity of our planet. Globalization, government policies, capitalism, colonialism, and other rapid social-ecological changes threaten the relationships between Indigenous Peoples and local communities and their environments, thereby challenging the continuity and dynamism of Indigenous and Local Knowledge (ILK). In this article, we contribute to the “World Scientists' Warning to Humanity,” issued by the Alliance of World Scientists, by exploring opportunities for sustaining ILK systems on behalf of the future stewardship of our planet. Our warning raises the alarm about the pervasive and ubiquitous erosion of knowledge and practice and the social and ecological consequences of this erosion. While ILK systems can be adaptable and resilient, the foundations of these knowledge systems are compromised by ongoing suppression, misrepresentation, appropriation, assimilation, disconnection, and destruction of biocultural heritage. Three case studies illustrate these processes and how protecting ILK is central to biocultural conservation. We conclude with 15 recommendations that call for the recognition and support of Indigenous Peoples and local communities and their knowledge systems. Enacting these recommendations will entail a transformative and sustained shift in how ILK systems, their knowledge holders, and their multiple expressions in lands and waters are recognized, affirmed, and valued. We appeal for urgent action to support the efforts of Indigenous Peoples and local communities around the world to maintain their knowledge systems, languages, stewardship rights, ties to lands and waters, and the biocultural integrity of their territories—on which we all depend.Peer reviewe
Reaction hijacking inhibition of Plasmodium falciparum asparagine tRNA synthetase
Malaria poses an enormous threat to human health. With ever increasing resistance to currently deployed drugs, breakthrough compounds with novel mechanisms of action are urgently needed. Here, we explore pyrimidine-based sulfonamides as a new low molecular weight inhibitor class with drug-like physical parameters and a synthetically accessible scaffold. We show that the exemplar, OSM-S-106, has potent activity against parasite cultures, low mammalian cell toxicity and low propensity for resistance development. In vitro evolution of resistance using a slow ramp-up approach pointed to the Plasmodium falciparum cytoplasmic asparaginyl-tRNA synthetase (PfAsnRS) as the target, consistent with our finding that OSM-S-106 inhibits protein translation and activates the amino acid starvation response. Targeted mass spectrometry confirms that OSM-S-106 is a pro-inhibitor and that inhibition of PfAsnRS occurs via enzyme-mediated production of an Asn-OSM-S-106 adduct. Human AsnRS is much less susceptible to this reaction hijacking mechanism. X-ray crystallographic studies of human AsnRS in complex with inhibitor adducts and docking of pro-inhibitors into a model of Asn-tRNA-bound PfAsnRS provide insights into the structure-activity relationship and the selectivity mechanism.</p
Submeter bathymetric mapping of volcanic and hydrothermal features on the East Pacific Rise crest at 9°50′N
Author Posting. © American Geophysical Union, 2007. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry Geophysics Geosystems 8 (2007): Q01006, doi:10.1029/2006GC001333.Recent advances in underwater vehicle navigation and sonar technology now permit detailed mapping of complex seafloor bathymetry found at mid-ocean ridge crests. Imagenex 881 (675 kHz) scanning sonar data collected during low-altitude (~5 m) surveys conducted with DSV Alvin were used to produce submeter resolution bathymetric maps of five hydrothermal vent areas at the East Pacific Rise (EPR) Ridge2000 Integrated Study Site (9°50′N, “bull's-eye”). Data were collected during 29 dives in 2004 and 2005 and were merged through a grid rectification technique to create high-resolution (0.5 m grid) composite maps. These are the first submeter bathymetric maps generated with a scanning sonar mounted on Alvin. The composite maps can be used to quantify the dimensions of meter-scale volcanic and hydrothermal features within the EPR axial summit trough (AST) including hydrothermal vent structures, lava pillars, collapse areas, the trough walls, and primary volcanic fissures. Existing Autonomous Benthic Explorer (ABE) bathymetry data (675 kHz scanning sonar) collected at this site provide the broader geologic context necessary to interpret the meter-scale features resolved in the composite maps. The grid rectification technique we employed can be used to optimize vehicle time by permitting the creation of high-resolution bathymetry maps from data collected during multiple, coordinated, short-duration surveys after primary dive objectives are met. This method can also be used to colocate future near-bottom sonar data sets within the high-resolution composite maps, enabling quantification of bathymetric changes associated with active volcanic, hydrothermal and tectonic processes.This work was supported by an NSF Ridge2000 fellowship
to V.L.F. and a Woods Hole Oceanographic Institution
fellowship supported by the W. Alan Clark Senior Scientist
Chair (D.J.F.). Funding was also provided by the Censsis
Engineering Research Center of the National Science Foundation
under grant EEC-9986821. Support for field and laboratory studies
was provided by the National Science Foundation under grants
OCE-9819261 (D.J.F. and M.T.), OCE-0096468 (D.J.F. and
T.S.), OCE-0328117 (SMC), OCE-0525863 (D.J.F. and
S.A.S.), OCE-0112737 ATM-0427220 (L.L.W.), and OCE-
0327261 and OCE-0328117 (T.S.). Additional support was
provided by The Edwin Link Foundation (J.C.K.)
Reaction hijacking inhibition of Plasmodium falciparum asparagine tRNA synthetase
Malaria poses an enormous threat to human health. With ever increasing resistance to currently deployed drugs, breakthrough compounds with novel mechanisms of action are urgently needed. Here, we explore pyrimidine-based sulfonamides as a new low molecular weight inhibitor class with drug-like physical parameters and a synthetically accessible scaffold. We show that the exemplar, OSM-S-106, has potent activity against parasite cultures, low mammalian cell toxicity and low propensity for resistance development. In vitro evolution of resistance using a slow ramp-up approach pointed to the Plasmodium falciparum cytoplasmic asparaginyl-tRNA synthetase (PfAsnRS) as the target, consistent with our finding that OSM-S-106 inhibits protein translation and activates the amino acid starvation response. Targeted mass spectrometry confirms that OSM-S-106 is a pro-inhibitor and that inhibition of PfAsnRS occurs via enzyme-mediated production of an Asn-OSM-S-106 adduct. Human AsnRS is much less susceptible to this reaction hijacking mechanism. X-ray crystallographic studies of human AsnRS in complex with inhibitor adducts and docking of pro-inhibitors into a model of Asn-tRNA-bound PfAsnRS provide insights into the structure-activity relationship and the selectivity mechanism
De novo assembly and characterization of a maternal and developmental transcriptome for the emerging model crustacean Parhyale hawaiensis
<p>Abstract</p> <p>Background</p> <p>Arthropods are the most diverse animal phylum, but their genomic resources are relatively few. While the genome of the branchiopod <it>Daphnia pulex </it>is now available, no other large-scale crustacean genomic resources are available for comparison. In particular, genomic resources are lacking for the most tractable laboratory model of crustacean development, the amphipod <it>Parhyale hawaiensis</it>. Insight into shared and divergent characters of crustacean genomes will facilitate interpretation of future developmental, biomedical, and ecological research using crustacean models.</p> <p>Results</p> <p>To generate a transcriptome enriched for maternally provided and zygotically transcribed developmental genes, we created cDNA from ovaries and embryos of <it>P. hawaiensis</it>. Using 454 pyrosequencing, we sequenced over 1.1 billion bases of this cDNA, and assembled them <it>de novo </it>to create, to our knowledge, the second largest crustacean genomic resource to date. We found an unusually high proportion of C2H2 zinc finger-containing transcripts, as has also been reported for the genome of the pea aphid <it>Acyrthosiphon pisum</it>. Consistent with previous reports, we detected trans-spliced transcripts, but found that they did not noticeably impact transcriptome assembly. Our assembly products yielded 19,067 unique BLAST hits against <b>nr </b>(E-value cutoff e-10). These included over 400 predicted transcripts with significant similarity to <it>D. pulex </it>sequences but not to sequences of any other animal. Annotation of several hundred genes revealed <it>P. hawaiensis </it>homologues of genes involved in development, gametogenesis, and a majority of the members of six major conserved metazoan signaling pathways.</p> <p>Conclusions</p> <p>The amphipod <it>P. hawaiensis </it>has higher transcript complexity than known insect transcriptomes, and trans-splicing does not appear to be a major contributor to this complexity. We discuss the importance of a reliable comparative genomic framework within which to consider findings from new crustacean models such as <it>D. pulex </it>and <it>P. hawaiensis</it>, as well as the need for development of further substantial crustacean genomic resources.</p
RNA-seq analyses of blood-induced changes in gene expression in the mosquito vector species, Aedes aegypti
<p>Abstract</p> <p>Background</p> <p>Hematophagy is a common trait of insect vectors of disease. Extensive genome-wide transcriptional changes occur in mosquitoes after blood meals, and these are related to digestive and reproductive processes, among others. Studies of these changes are expected to reveal molecular targets for novel vector control and pathogen transmission-blocking strategies. The mosquito <it>Aedes aegypti </it>(Diptera, Culicidae), a vector of Dengue viruses, Yellow Fever Virus (YFV) and Chikungunya virus (CV), is the subject of this study to look at genome-wide changes in gene expression following a blood meal.</p> <p>Results</p> <p>Transcriptional changes that follow a blood meal in <it>Ae. aegypti </it>females were explored using RNA-seq technology. Over 30% of more than 18,000 investigated transcripts accumulate differentially in mosquitoes at five hours after a blood meal when compared to those fed only on sugar. Forty transcripts accumulate only in blood-fed mosquitoes. The list of regulated transcripts correlates with an enhancement of digestive activity and a suppression of environmental stimuli perception and innate immunity. The alignment of more than 65 million high-quality short reads to the <it>Ae. aegypti </it>reference genome permitted the refinement of the current annotation of transcript boundaries, as well as the discovery of novel transcripts, exons and splicing variants. <it>Cis</it>-regulatory elements (CRE) and <it>cis</it>-regulatory modules (CRM) enriched significantly at the 5'end flanking sequences of blood meal-regulated genes were identified.</p> <p>Conclusions</p> <p>This study provides the first global view of the changes in transcript accumulation elicited by a blood meal in <it>Ae. aegypti </it>females. This information permitted the identification of classes of potentially co-regulated genes and a description of biochemical and physiological events that occur immediately after blood feeding. The data presented here serve as a basis for novel vector control and pathogen transmission-blocking strategies including those in which the vectors are modified genetically to express anti-pathogen effector molecules.</p
Search for subsolar-mass black hole binaries in the second part of Advanced LIGO’s and Advanced Virgo’s third observing run
We describe a search for gravitational waves from compact binaries with at least one component with mass 0.2–1.0 M and mass
ratio q ≥ 0.1 in Advanced Laser Interferometer Gravitational-Wave Observatory (LIGO) and Advanced Virgo data collected
between 2019 November 1, 15:00 UTC and 2020 March 27, 17:00 UTC. No signals were detected. The most significant candidate
has a false alarm rate of 0.2 yr−1. We estimate the sensitivity of our search over the entirety of Advanced LIGO’s and Advanced
Virgo’s third observing run, and present the most stringent limits to date on the merger rate of binary black holes with at least one
subsolar-mass component. We use the upper limits to constrain two fiducial scenarios that could produce subsolar-mass black
holes: primordial black holes (PBH) and a model of dissipative dark matter. The PBH model uses recent prescriptions for the
merger rate of PBH binaries that include a rate suppression factor to effectively account for PBH early binary disruptions. If the
PBHs are monochromatically distributed, we can exclude a dark matter fraction in PBHs fPBH 0.6 (at 90 per cent confidence)
in the probed subsolar-mass range. However, if we allow for broad PBH mass distributions, we are unable to rule out fPBH = 1.
For the dissipative model, where the dark matter has chemistry that allows a small fraction to cool and collapse into black holes,
we find an upper bound fDBH < 10−5 on the fraction of atomic dark matter collapsed into black holes
Search for subsolar-mass black hole binaries in the second part of Advanced LIGO's and Advanced Virgo's third observing run
We describe a search for gravitational waves from compact binaries with at
least one component with mass 0.2 -- and mass ratio in Advanced LIGO and Advanced Virgo data collected between 1 November
2019, 15:00 UTC and 27 March 2020, 17:00 UTC. No signals were detected. The
most significant candidate has a false alarm rate of 0.2 . We
estimate the sensitivity of our search over the entirety of Advanced LIGO's and
Advanced Virgo's third observing run, and present the most stringent limits to
date on the merger rate of binary black holes with at least one subsolar-mass
component. We use the upper limits to constrain two fiducial scenarios that
could produce subsolar-mass black holes: primordial black holes (PBH) and a
model of dissipative dark matter. The PBH model uses recent prescriptions for
the merger rate of PBH binaries that include a rate suppression factor to
effectively account for PBH early binary disruptions. If the PBHs are
monochromatically distributed, we can exclude a dark matter fraction in PBHs
(at 90% confidence) in the probed subsolar-mass
range. However, if we allow for broad PBH mass distributions we are unable to
rule out . For the dissipative model, where the dark matter
has chemistry that allows a small fraction to cool and collapse into black
holes, we find an upper bound on the fraction of
atomic dark matter collapsed into black holes.Comment: https://dcc.ligo.org/P220013
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