17 research outputs found
Recommended from our members
Genetic variation across RNA metabolism and cell death gene networks is implicated in the semantic variant of primary progressive aphasia
The semantic variant of primary progressive aphasia (svPPA) is a clinical syndrome characterized by neurodegeneration and progressive loss of semantic knowledge. Unlike many other forms of frontotemporal lobar degeneration (FTLD), svPPA has a highly consistent underlying pathology composed of TDP-43 (a regulator of RNA and DNA transcription metabolism). Previous genetic studies of svPPA are limited by small sample sizes and a paucity of common risk variants. Despite this, svPPA\xe2\x80\x99s relatively homogenous clinicopathologic phenotype makes it an ideal investigative model to examine genetic processes that may drive neurodegenerative disease. In this study, we used GWAS metadata, tissue samples from pathologically confirmed frontotemporal lobar degeneration, and in silico techniques to identify and characterize protein interaction networks associated with svPPA risk. We identified 64 svPPA risk genes that interact at the protein level. The protein pathways represented in this svPPA gene network are critical regulators of RNA metabolism and cell death, such as SMAD proteins and NOTCH1. Many of the genes in this network are involved in TDP-43 metabolism. Contrary to the conventional notion that svPPA is a clinical syndrome with few genetic risk factors, our analyses show that svPPA risk is complex and polygenic in nature. Risk for svPPA is likely driven by multiple common variants in genes interacting with TDP-43, along with cell death,x` working in combination to promote neurodegeneration
Recommended from our members
The Limits of Visual Resolution
Visual resolution, the ability to see fine spatial detail, emerges from the capacities of both the eye and the brain. A great deal of insight into the anatomical and physiological basis of human visual resolution has been gained since Helmholtz first proposed his sampling theory of visual resolution. Anatomical, physiological and psychophysical investigations have revealed in great detail the properties of the biological structures underlying visual resolution and identified many of the optical, retinal, and cortical factors that govern the limits of visual resolution. However, technological limitations have long prevented researchers from examining both the structure and function of the visual system simultaneously in the living eye. The microscopic photoreceptors of the retina have been inaccessible to optical examination, preventing high quality measurements of both visual resolution and retinal anatomy from being obtained in the same eyes. The present studies investigated the relationship between the optical, retinal, and cortical factors that govern visual resolution in humans. These experiments employed adaptive optics scanning laser ophthalmoscopy (AOSLO) as a tool to study how these factors govern visual resolution in normal and diseased eyes. The AOSLO is an ideal tool for studying the limits of vision because of its ability to present complex stimuli to the retina that are of higher optical quality than the visual system has ever experienced, while simultaneously imaging the underlying cone photoreceptor mosaic on a microscopic scale.Adaptive optics correction of ocular aberrations allowed observers to achieve immediate and significant improvements in visual resolution. Training was not required to achieve this benefit, which allowed the resolving capacity of the retinal and cortical visual system to be assessed unobstructed by the optics of the eye. Not all participants in these studies benefited to the same extent from AO correction. Visual resolution was found to be significantly poorer in low myopia as compared to emmetropia, despite the similar optical quality afforded by AO correction, showing that retinal and cortical changes in myopia caused the observed deficit. Simultaneous imaging and visual resolution testing determined the precise relationship between the spatial sampling limit of the cone mosaic and visual resolution across the human fovea. These studies revealed that the spatial sampling limit of the cone mosaic largely governs visual resolution at the center of the fovea for normal eyes, but that outside the foveal center visual resolution falls off at a greater rate than predicted by cone spacing and is governed by the spatial sampling limit of the mosaic of midget retinal ganglion cells.Significant differences between otherwise normally appearing observers were revealed using AOSLO, showing the power of visual resolution testing after AO correction for detecting small changes in the visual system resulting from disease. Significant retinal changes were revealed in female carriers of a rare X-linked genetic mutation in the L and M opsin gene array that causes blue cone monochromacy (the loss of all L and M cone function) in affected males. Retinal findings from AO imaging provided insight into the development and function of the carrier retina. Although carriers had visual resolution within the normal range when tested clinically, visual resolution testing in AOSLO revealed significantly reduced visual resolution compared to normal eyes. Resolution testing across the fovea in normal and diseased eyes provided insight into the relationship between cones, ganglion cells and visual resolution across the visual field. Retinal imaging showed that carriers had fairly normal cone topography despite peak cone density that was ~50% lower than normal; showing that cones destined to express a non-functional photopigment degenerated early in development. Drastic reductions in visual resolution across the fovea in the carrier are best explained by ganglion cell loss that resulted from the loss of cones in the carrier. The relationship between resolution and the spatial sampling limit of the carrier cone mosaic was similar to what was predicted for normal eyes, suggesting an organizing principle in the visual system whereby cone density is the primary determinant of the retinal circuitry that governs visual resolution across the visual field. Together, these studies provide an important contribution to the understanding of the limits of human visual resolution
NANCY: Next-generation All-sky Near-infrared Community surveY
International audienceThe Nancy Grace Roman Space Telescope is capable of delivering an unprecedented all-sky, high-spatial resolution, multi-epoch infrared map to the astronomical community. This opportunity arises in the midst of numerous ground- and space-based surveys that will provide extensive spectroscopy and imaging together covering the entire sky (such as Rubin/LSST, Euclid, UNIONS, SPHEREx, DESI, SDSS-V, GALAH, 4MOST, WEAVE, MOONS, PFS, UVEX, NEO Surveyor, etc.). Roman can uniquely provide uniform high-spatial-resolution (~0.1 arcsec) imaging over the entire sky, vastly expanding the science reach and precision of all of these near-term and future surveys. This imaging will not only enhance other surveys, but also facilitate completely new science. By imaging the full sky over two epochs, Roman can measure the proper motions for stars across the entire Milky Way, probing 100 times fainter than Gaia out to the very edge of the Galaxy. Here, we propose NANCY: a completely public, all-sky survey that will create a high-value legacy dataset benefiting innumerable ongoing and forthcoming studies of the universe. NANCY is a pure expression of Roman's potential: it images the entire sky, at high spatial resolution, in a broad infrared bandpass that collects as many photons as possible. The majority of all ongoing astronomical surveys would benefit from incorporating observations of NANCY into their analyses, whether these surveys focus on nearby stars, the Milky Way, near-field cosmology, or the broader universe
Dark Matter Science in the Era of LSST
Astrophysical observations currently provide the only robust, empirical measurements of dark matter. In the coming decade, astrophysical observations will guide other experimental efforts, while simultaneously probing unique regions of dark matter parameter space. This white paper summarizes astrophysical observations that can constrain the fundamental physics of dark matter in the era of LSST. We describe how astrophysical observations will inform our understanding of the fundamental properties of dark matter, such as particle mass, self-interaction strength, non-gravitational interactions with the Standard Model, and compact object abundances. Additionally, we highlight theoretical work and experimental/observational facilities that will complement LSST to strengthen our understanding of the fundamental characteristics of dark matter
NANCY: Next-generation All-sky Near-infrared Community surveY
International audienceThe Nancy Grace Roman Space Telescope is capable of delivering an unprecedented all-sky, high-spatial resolution, multi-epoch infrared map to the astronomical community. This opportunity arises in the midst of numerous ground- and space-based surveys that will provide extensive spectroscopy and imaging together covering the entire sky (such as Rubin/LSST, Euclid, UNIONS, SPHEREx, DESI, SDSS-V, GALAH, 4MOST, WEAVE, MOONS, PFS, UVEX, NEO Surveyor, etc.). Roman can uniquely provide uniform high-spatial-resolution (~0.1 arcsec) imaging over the entire sky, vastly expanding the science reach and precision of all of these near-term and future surveys. This imaging will not only enhance other surveys, but also facilitate completely new science. By imaging the full sky over two epochs, Roman can measure the proper motions for stars across the entire Milky Way, probing 100 times fainter than Gaia out to the very edge of the Galaxy. Here, we propose NANCY: a completely public, all-sky survey that will create a high-value legacy dataset benefiting innumerable ongoing and forthcoming studies of the universe. NANCY is a pure expression of Roman's potential: it images the entire sky, at high spatial resolution, in a broad infrared bandpass that collects as many photons as possible. The majority of all ongoing astronomical surveys would benefit from incorporating observations of NANCY into their analyses, whether these surveys focus on nearby stars, the Milky Way, near-field cosmology, or the broader universe
NANCY: Next-generation All-sky Near-infrared Community surveY
International audienceThe Nancy Grace Roman Space Telescope is capable of delivering an unprecedented all-sky, high-spatial resolution, multi-epoch infrared map to the astronomical community. This opportunity arises in the midst of numerous ground- and space-based surveys that will provide extensive spectroscopy and imaging together covering the entire sky (such as Rubin/LSST, Euclid, UNIONS, SPHEREx, DESI, SDSS-V, GALAH, 4MOST, WEAVE, MOONS, PFS, UVEX, NEO Surveyor, etc.). Roman can uniquely provide uniform high-spatial-resolution (~0.1 arcsec) imaging over the entire sky, vastly expanding the science reach and precision of all of these near-term and future surveys. This imaging will not only enhance other surveys, but also facilitate completely new science. By imaging the full sky over two epochs, Roman can measure the proper motions for stars across the entire Milky Way, probing 100 times fainter than Gaia out to the very edge of the Galaxy. Here, we propose NANCY: a completely public, all-sky survey that will create a high-value legacy dataset benefiting innumerable ongoing and forthcoming studies of the universe. NANCY is a pure expression of Roman's potential: it images the entire sky, at high spatial resolution, in a broad infrared bandpass that collects as many photons as possible. The majority of all ongoing astronomical surveys would benefit from incorporating observations of NANCY into their analyses, whether these surveys focus on nearby stars, the Milky Way, near-field cosmology, or the broader universe
NANCY: Next-generation All-sky Near-infrared Community surveY
International audienceThe Nancy Grace Roman Space Telescope is capable of delivering an unprecedented all-sky, high-spatial resolution, multi-epoch infrared map to the astronomical community. This opportunity arises in the midst of numerous ground- and space-based surveys that will provide extensive spectroscopy and imaging together covering the entire sky (such as Rubin/LSST, Euclid, UNIONS, SPHEREx, DESI, SDSS-V, GALAH, 4MOST, WEAVE, MOONS, PFS, UVEX, NEO Surveyor, etc.). Roman can uniquely provide uniform high-spatial-resolution (~0.1 arcsec) imaging over the entire sky, vastly expanding the science reach and precision of all of these near-term and future surveys. This imaging will not only enhance other surveys, but also facilitate completely new science. By imaging the full sky over two epochs, Roman can measure the proper motions for stars across the entire Milky Way, probing 100 times fainter than Gaia out to the very edge of the Galaxy. Here, we propose NANCY: a completely public, all-sky survey that will create a high-value legacy dataset benefiting innumerable ongoing and forthcoming studies of the universe. NANCY is a pure expression of Roman's potential: it images the entire sky, at high spatial resolution, in a broad infrared bandpass that collects as many photons as possible. The majority of all ongoing astronomical surveys would benefit from incorporating observations of NANCY into their analyses, whether these surveys focus on nearby stars, the Milky Way, near-field cosmology, or the broader universe
NANCY: Next-generation All-sky Near-infrared Community surveY
International audienceThe Nancy Grace Roman Space Telescope is capable of delivering an unprecedented all-sky, high-spatial resolution, multi-epoch infrared map to the astronomical community. This opportunity arises in the midst of numerous ground- and space-based surveys that will provide extensive spectroscopy and imaging together covering the entire sky (such as Rubin/LSST, Euclid, UNIONS, SPHEREx, DESI, SDSS-V, GALAH, 4MOST, WEAVE, MOONS, PFS, UVEX, NEO Surveyor, etc.). Roman can uniquely provide uniform high-spatial-resolution (~0.1 arcsec) imaging over the entire sky, vastly expanding the science reach and precision of all of these near-term and future surveys. This imaging will not only enhance other surveys, but also facilitate completely new science. By imaging the full sky over two epochs, Roman can measure the proper motions for stars across the entire Milky Way, probing 100 times fainter than Gaia out to the very edge of the Galaxy. Here, we propose NANCY: a completely public, all-sky survey that will create a high-value legacy dataset benefiting innumerable ongoing and forthcoming studies of the universe. NANCY is a pure expression of Roman's potential: it images the entire sky, at high spatial resolution, in a broad infrared bandpass that collects as many photons as possible. The majority of all ongoing astronomical surveys would benefit from incorporating observations of NANCY into their analyses, whether these surveys focus on nearby stars, the Milky Way, near-field cosmology, or the broader universe
State of the climate in 2010
Several large-scale climate patterns influenced climate conditions and weather patterns across the globe during 2010. The transition from a warm El Nino phase at the beginning of the year to a cool La Nina phase by July contributed to many notable events, ranging from record wetness across much of Australia to historically low Eastern Pacific basin and near-record high North Atlantic basin hurricane activity. The remaining five main hurricane basins experienced below-to well-below-normal tropical cyclone activity. The negative phase of the Arctic Oscillation was a major driver of Northern Hemisphere temperature patterns during 2009/10 winter and again in late 2010. It contributed to record snowfall and unusually low temperatures over much of northern Eurasia and parts of the United States, while bringing above-normal temperatures to the high northern latitudes. The February Arctic Oscillation Index value was the most negative since records began in 1950. The 2010 average global land and ocean surface temperature was among the two warmest years on record. The Arctic continued to warm at about twice the rate of lower latitudes. The eastern and tropical Pacific Ocean cooled about 1 C from 2009 to 2010, reflecting the transition from the 2009/10 El Nino to the 2010/11 La Nina. Ocean heat fluxes contributed to warm sea surface temperature anomalies in the North Atlantic and the tropical Indian and western Pacific Oceans. Global integrals of upper ocean heat content for the past several years have reached values consistently higher than for all prior times in the record, demonstrating the dominant role of the ocean in the Earth's energy budget. Deep and abyssal waters of Antarctic origin have also trended warmer on average since the early 1990s. Lower tropospheric temperatures typically lag ENSO surface fluctuations by two to four months, thus the 2010 temperature was dominated by the warm phase El Nino conditions that occurred during the latter half of 2009 and early 2010 and was second warmest on record. The stratosphere continued to be anomalously cool. Annual global precipitation over land areas was about five percent above normal. Precipitation over the ocean was drier than normal after a wet year in 2009. Overall, saltier (higher evaporation) regions of the ocean surface continue to be anomalously salty, and fresher (higher precipitation) regions continue to be anomalously fresh. This salinity pattern, which has held since at least 2004, suggests an increase in the hydrological cycle. Sea ice conditions in the Arctic were significantly different than those in the Antarctic during the year. The annual minimum ice extent in the Arctic reached in September was the third lowest on record since 1979. In the Antarctic, zonally averaged sea ice extent reached an all-time record maximum from mid-June through late August and again from mid-November through early December. Corresponding record positive Southern Hemisphere Annular Mode Indices influenced the Antarctic sea ice extents. Greenland glaciers lost more mass than any other year in the decade-long record. The Greenland Ice Sheet lost a record amount of mass, as the melt rate was the highest since at least 1958, and the area and duration of the melting was greater than any year since at least 1978. High summer air temperatures and a longer melt season also caused a continued increase in the rate of ice mass loss from small glaciers and ice caps in the Canadian Arctic. Coastal sites in Alaska show continuous permafrost warming and sites in Alaska, Canada, and Russia indicate more significant warming in relatively cold permafrost than in warm permafrost in the same geographical area. With regional differences, permafrost temperatures are now up to 2 C warmer than they were 20 to 30 years ago. Preliminary data indicate there is a high probability that 2010 will be the 20th consecutive year that alpine glaciers have lost mass. Atmospheric greenhouse gas concentrations continued to rise and ozone depleting substances continued to decrease. Carbon dioxide increased by 2.60 ppm in 2010, a rate above both the 2009 and the 1980-2010 average rates. The global ocean carbon dioxide uptake for the 2009 transition period from La Nina to El Nino conditions, the most recent period for which analyzed data are available, is estimated to be similar to the long-term average. The 2010 Antarctic ozone hole was among the lowest 20% compared with other years since 1990, a result of warmer-than-average temperatures in the Antarctic stratosphere during austral winter between mid-July and early September