113 research outputs found
Rb-Sr, Sm-Nd and Ar-Ar isotopic systematics of Antarctic nakhlite Yamato 000593
sotopic analysis of the newly found Antarctic nakhlite Yamato (Y) 000593 yields a Rb-Sr age of 1.30±0.02Ga with an initial ^(87)Sr/^(86)Sr of 0.702525±0.000027, a Sm-Nd age of 1.31±0.03Ga with an initial ε_(Nd) of + 16.0±0.2 and an Ar-Ar isochron age of <=1.36Ga. The concordancy of these three ages and Rb-Sr and Sm-Nd initial isotopic signatures strongly suggest that Y000593 crystallized from low Rb/Sr, light REE-depleted source materials ~1.31Ga ago. The crystallization age of Y000593 is compared with the age data of non-Antarctic nakhlites (Nakhla, Governador Valadares, Lafayette and Northwest Africa 998) and Chassigny. The initial Sr and Nd isotopic signatures suggest that Lafayette and Y000593 were co-magmatic or at least came from very similar magmas. Cosmogenic ^(36)Ar concentrations in Y000593 resemble those in other nakhlites. The similarities in crystallization and ejection ages and in petrologic features suggest the nakhlites were derived from similar source regions, and launch pairing of nakhlites and Chassigny. The Rb-Sr data for Y000593 show that the isotopic system is disturbed by pre-terrestrial alteration of olivine. Although many of the acid-leached residues of mineral fractions fall along the 1.30Ga Rb-Sr isochron, leached olivine does not. This indicates the lack of isotopic equilibrium between the olivine fractions and the secondary alteration phases. A tie-line between two olivine leachates provides a calculated "age" of 650±80Ma with an initial ^(87)Sr/^(86)Sr of ~0.70465, which gives a hint for the isotopic signatures of local brine as well as the timing of an aqueous alteration event on the Martian surface
Effects of the electromagnetic field used in hydrocarbon surveys on marine organisms
Controlled Source Electromagnetics (CSEM) technology has been used in the exploration for hydrocarbon reservoirs. It consists of an electric dipole source which is towed horizontally 30-50 m above the seabed or 10 m below the surface. As the electromagnetic (EM) signal propagates through the subsurface it may affect marine organisms that are electro- or magneto-sensitive. A device simulating these conditions (corresponding to three different exposure levels, low, strong, near field) was built to test the effect of EM on marine organisms in laboratory conditions.) Sandeel (Ammodytes tobianus) adults were filmed during a 15-minute near-field EM exposure but showed no significant changes in their behavior, nor any increased mortality. Haddock juveniles (Melanogrammus aeglefinus) were first exposed for 15 minutes to either one of the three EM levels then filmed and tested for magnetic orientation. None of the treatments caused mortality in fish. Juvenile haddock showed significant orientation according to the magnetic field but only after exposure to low and strong EM fields. They also showed a significantly reduced swimming speed following exposure to EM with intensities equivalent to distances of 100 (strong) and 1000 m (low) from the source with an average reduction in speed of 24%. Mean instantaneous swimming velocities of haddock decreased from 1.18 pixel/s (control) to 0.86 and 0.80 pixel/s after exposure to low and strong field levels respectively (GLM estimates), representing speed reductions of 27% and 32% after exposure to each respective level. Changes in swimming speed may affect dispersal of juveniles. However, it is unknown whether the decrease was a physiological or behavioural response. Therefore, it is not possible to make unequivocal conclusions about detrimental effects of CSEM at the population level.publishedVersio
Association of Mitochondrial DNA Copy Number With Brain MRI Markers and Cognitive Function: A Meta-Analysis of Community-Based Cohorts
BACKGROUND AND OBJECTIVES: Previous studies suggest that lower mitochondrial DNA (mtDNA) copy number (CN) is associated with neurodegenerative diseases. However, whether mtDNA CN in whole blood is related to endophenotypes of Alzheimer disease (AD) and AD-related dementia (AD/ADRD) needs further investigation. We assessed the association of mtDNA CN with cognitive function and MRI measures in community-based samples of middle-aged to older adults.
METHODS: We included dementia-free participants from 9 diverse community-based cohorts with whole-genome sequencing in the Trans-Omics for Precision Medicine (TOPMed) program. Circulating mtDNA CN was estimated as twice the ratio of the average coverage of mtDNA to nuclear DNA. Brain MRI markers included total brain, hippocampal, and white matter hyperintensity volumes. General cognitive function was derived from distinct cognitive domains. We performed cohort-specific association analyses of mtDNA CN with AD/ADRD endophenotypes assessed within ±5 years (i.e., cross-sectional analyses) or 5-20 years after blood draw (i.e., prospective analyses) adjusting for potential confounders. We further explored associations stratified by sex and age (≥60 years). Fixed-effects or sample size-weighted meta-analyses were performed to combine results. Finally, we performed mendelian randomization (MR) analyses to assess causality.
RESULTS: We included up to 19,152 participants (mean age 59 years, 57% women). Higher mtDNA CN was cross-sectionally associated with better general cognitive function (β = 0.04; 95% CI 0.02-0.06) independent of age, sex, batch effects, race/ethnicity, time between blood draw and cognitive evaluation, cohort-specific variables, and education. Additional adjustment for blood cell counts or cardiometabolic traits led to slightly attenuated results. We observed similar significant associations with cognition in prospective analyses, although of reduced magnitude. We found no significant associations between mtDNA CN and brain MRI measures in meta-analyses. MR analyses did not reveal a causal relation between mtDNA CN in blood and cognition.
DISCUSSION: Higher mtDNA CN in blood is associated with better current and future general cognitive function in large and diverse communities across the United States. Although MR analyses did not support a causal role, additional research is needed to assess causality. Circulating mtDNA CN could serve nevertheless as a biomarker of current and future cognitive function in the community
SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues.
There is pressing urgency to understand the pathogenesis of the severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2), which causes the disease COVID-19. SARS-CoV-2 spike (S) protein binds angiotensin-converting enzyme 2 (ACE2), and in concert with host proteases, principally transmembrane serine protease 2 (TMPRSS2), promotes cellular entry. The cell subsets targeted by SARS-CoV-2 in host tissues and the factors that regulate ACE2 expression remain unknown. Here, we leverage human, non-human primate, and mouse single-cell RNA-sequencing (scRNA-seq) datasets across health and disease to uncover putative targets of SARS-CoV-2 among tissue-resident cell subsets. We identify ACE2 and TMPRSS2 co-expressing cells within lung type II pneumocytes, ileal absorptive enterocytes, and nasal goblet secretory cells. Strikingly, we discovered that ACE2 is a human interferon-stimulated gene (ISG) in vitro using airway epithelial cells and extend our findings to in vivo viral infections. Our data suggest that SARS-CoV-2 could exploit species-specific interferon-driven upregulation of ACE2, a tissue-protective mediator during lung injury, to enhance infection
Exome chip analysis identifies low-frequency and rare variants in MRPL38 for white matter hyperintensities on brain MRI
International audienc
Skeletal Toxicity Associated with Chronic Ethanol Exposure in a Rat Model Using Total Enteral Nutrition
Cerebral small vessel disease genomics and its implications across the lifespan
White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.Peer reviewe
Novel genetic loci associated with hippocampal volume
The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness
Genetic architecture of subcortical brain structures in 38,851 individuals
Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease
Genetic architecture of subcortical brain structures in 38,851 individuals
Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease
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