Paleoclimatic reconstructions in western Canada from boreholetemperature logs: surface air temperature forcing and groundwater flow

International audienceModelling of surface temperature change effect on temperature vs.~depth and temperature-depth logs in Western Canada Sedimentary Basin show that SAT (surface air temperature) forcing is the main driving factor for the underground temperature changes diffusing with depth. It supports the validity of the basic hypothesis of borehole temperature paleoclimatology, namely that the ground surface temperature is systematically coupled with the air temperature in the longer term (decades, centuries). While the highest groundwater recharge rate used in the modelling suggests that for this extreme case some of the observed curvature in the profile, could be due to groundwater flow, it is more likely that the low recharge rates in this semi-arid region would have minimal impact. We conclude that surface temperature forcing is responsible for most of the observed anomalous temperature profile

Effective mobilities in pseudomorphic Si/SiGe/Si p-channel metal-oxide-semiconductor field-effect transistors with thin silicon capping layers

The room-temperature effective mobilities of pseudomorphic Si/Si0.64Ge0.36/Si p-metal-oxidesemiconductor field effect transistors are reported. The peak mobility in the buried SiGe channel increases with silicon cap thickness. It is argued that SiO2/Si interface roughness is a major source of scattering in these devices, which is attenuated for thicker silicon caps. It is also suggested that segregated Ge in the silicon cap interferes with the oxidation process, leading to increased SiO2/Si interface roughness in the case of thin silicon caps

Low-Temperature Sulfidic-Ice Microbial Communities, Borup Fiord Pass, Canadian High Arctic

A sulfur-dominated supraglacial spring system found at Borup Fiord Pass (BFP), Ellesmere Island, Nunavut, Canada, is a unique sulfur-on-ice system expressed along the toe of a glacier. BFP has an intermittent flowing, subsurface-derived, glacial spring that creates a large white-yellow icing (aufeis) that extends down-valley. Over field campaigns in 2014, 2016, and 2017, numerous samples were collected and analyzed for both microbial community composition and aqueous geochemistry. Samples were collected from multiple site types: spring discharge fluid, aufeis (spring-derived ice), melt pools with sedimented cryoconite material, and mineral precipitate scrapings, to probe how microbial communities differed between site types in a dynamic freeze/thaw sulfur-rich system. Dissolved sulfate varied between 0.07 and 11.6 mM and was correlated with chloride concentrations, where the fluids were saltiest among spring fluids. The highest sulfate samples exhibited high dissolved sulfide values between 0.22 and 2.25 mM. 16S rRNA gene sequencing from melt pool and aufeis samples from the 2014 campaign were highly abundant in operational taxonomic units (OTUs) closely related to sulfur-oxidizing microorganisms (SOM; Sulfurimonas, Sulfurovum, and Sulfuricurvum). Subsequent sampling 2 weeks later had fewer SOMs and showed an increased abundance of the genus Flavobacterium. Desulfocapsa, an organism that specializes in the disproportionation of inorganic sulfur compounds was also found. Samples from 2016 and 2017 revealed that microorganisms present were highly similar in community composition to 2014 samples, primarily echoed by the continued presence of Flavobacterium sp. Results suggest that while there may be acute events where sulfur cycling organisms dominate, a basal community structure appears to dominate over time and site type. These results further enhance our knowledge of low-temperature sulfur systems on Earth, and help to guide the search for potential life on extraterrestrial worlds, such as Europa, where similar low-temperature sulfur-rich conditions may exist

Continental weathering and recovery from ocean nutrient stress during the Early Triassic Biotic Crisis

Following the latest Permian extinction ∼252 million years ago, normal marine and terrestrial ecosystems did not recover for another 5-9 million years. The driver(s) for the Early Triassic biotic crisis, marked by high atmospheric CO2 concentration, extreme ocean warming, and marine anoxia, remains unclear. Here we constrain the timing of authigenic K-bearing mineral formation extracted from supergene weathering profiles of NW-Pangea by Argon geochronology, to demonstrate that an accelerated hydrological cycle causing intense chemical alteration of the continents occurred between ∼254 and 248 Ma, and continued throughout the Triassic period. We show that enhanced ocean nutrient supply from this intense continental weathering did not trigger increased ocean productivity during the Early Triassic biotic crisis, due to strong thermal ocean stratification off NW Pangea. Nitrogen isotope constraints suggest, instead, that full recovery from ocean nutrient stress, despite some brief amelioration ∼1.5 million years after the latest Permian extinction, did not commence until climate cooling revitalized the global upwelling systems and ocean mixing ∼10 million years after the mass extinction

The evolutionary history of common genetic variants influencing human cortical surface area

Structural brain changes along the lineage leading to modern Homo sapiens contributed to our distinctive cognitive and social abilities. However, the evolutionarily relevant molecular variants impacting key aspects of neuroanatomy are largely unknown. Here, we integrate evolutionary annotations of the genome at diverse timescales with common variant associations from large-scale neuroimaging genetic screens. We find that alleles with evidence of recent positive polygenic selection over the past 2000–3000 years are associated with increased surface area (SA) of the entire cortex, as well as specific regions, including those involved in spoken language and visual processing. Therefore, polygenic selective pressures impact the structure of specific cortical areas even over relatively recent timescales. Moreover, common sequence variation within human gained enhancers active in the prenatal cortex is associated with postnatal global SA. We show that such variation modulates the function of a regulatory element of the developmentally relevant transcription factor HEY2 in human neural progenitor cells and is associated with structural changes in the inferior frontal cortex. These results indicate that non-coding genomic regions active during prenatal cortical development are involved in the evolution of human brain structure and identify novel regulatory elements and genes impacting modern human brain structure

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors

Genetic determinants of cortical structure (thickness, surface area and volumes) among disease free adults in the CHARGE Consortium

Cortical thickness, surface area and volumes (MRI cortical measures) vary with age and cognitive function, and in neurological and psychiatric diseases. We examined heritability, genetic correlations and genome-wide associations of cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprised 22,824 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the United Kingdom Biobank. Significant associations were replicated in the Enhancing Neuroimaging Genetics through Meta-analysis (ENIGMA) consortium, and their biological implications explored using bioinformatic annotation and pathway analyses. We identified genetic heterogeneity between cortical measures and brain regions, and 160 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There was enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging

Social competence in parents increases children’s educational attainment:Replicable genetically-mediated effects of parenting revealed by non-transmitted DNA

We recently reported an association of offspring educational attainment with polygenic risk scores (PRS) computed on parent's non-transmitted alleles for educational attainment using the second GWAS meta-analysis article on educational attainment published by the Social Science Genetic Association Consortium. Here we test the replication of these findings using a more powerful PRS from the third GWAS meta-analysis article by the Consortium. Each of the key findings of our previous paper is replicated using this improved PRS (N = 2335 adolescent twins and their genotyped parents). The association of children's attainment with their own PRS increased substantially with the standardized effect size, moving from β = 0.134, 95% CI = 0.079, 0.188 for EA2, to β = 0.223, 95% CI = 0.169, 0.278, p <.001, for EA3. Parent's PRS again predicted the socioeconomic status (SES) they provided to their offspring and increased from β = 0.201, 95% CI = 0.147, 0.256 to β = 0.286, 95% CI = 0.239, 0.333. Importantly, the PRS for alleles not transmitted to their offspring - therefore acting via the parenting environment - was increased in effect size from β = 0.058, 95% CI = 0.003, 0.114 to β = 0.067, 95% CI = 0.012, 0.122, p =.016. As previously found, this non-transmitted genetic effect was fully accounted for by parental SES. The findings reinforce the conclusion that genetic effects of parenting are substantial, explain approximately one-third the magnitude of an individual's own genetic inheritance and are mediated by parental socioeconomic competence

Cellular Active N-Hydroxyurea FEN1 Inhibitors Block Substrate Entry to the Active Site

The structure-specific nuclease human flap endonuclease-1 (hFEN1) plays a key role in DNA replication and repair and may be of interest as an oncology target. We present the first crystal structure of inhibitor-bound hFEN1 and show a cyclic N-hydroxyurea bound in the active site coordinated to two magnesium ions. Three such compounds had similar IC50 values but differed subtly in mode of action. One had comparable affinity for protein and protein– substrate complex and prevented reaction by binding to active site catalytic metal ions, blocking the unpairing of substrate DNA necessary for reaction. Other compounds were more competitive with substrate. Cellular thermal shift data showed engagement of both inhibitor types with hFEN1 in cells with activation of the DNA damage response evident upon treatment. However, cellular EC50s were significantly higher than in vitro inhibition constants and the implications of this for exploitation of hFEN1 as a drug target are discussed

Dynamic anoxic ferruginous conditions during the end-Permian mass extinction and recovery

The end-Permian mass extinction, ~252 million years ago, is notable for a complex recovery period of ~5 Myr. Widespread euxinic (anoxic and sulfidic) oceanic conditions have been proposed as both extinction mechanism and explanation for the protracted recovery period, yet the vertical distribution of anoxia in the water column and its temporal dynamics through this time period are poorly constrained. Here we utilize Fe–S–C systematics integrated with palaeontological observations to reconstruct a complete ocean redox history for the Late Permian to Early Triassic, using multiple sections across a shelf-to-basin transect on the Arabian Margin (Neo-Tethyan Ocean). In contrast to elsewhere, we show that anoxic non-sulfidic (ferruginous), rather than euxinic, conditions were prevalent in the Neo-Tethys. The Arabian Margin record demonstrates the repeated expansion of ferruginous conditions with the distal slope being the focus of anoxia at these times, as well as short-lived episodes of oxia that supported diverse biota