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52 Research products, page 1 of 6

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  • Publication . Conference object . 2016
    Open Access
    Authors: 
    Joppe W. Bos; Craig Costello; Léo Ducas; Ilya Mironov; Michael Naehrig; Valeria Nikolaenko; Ananth Raghunathan; Douglas Stebila;
    Publisher: ACM
    Country: Netherlands
    Project: NSERC , ARC | Internet authentication p... (DP130104304), EC | PQCRYPTO (645622)

    Lattice-based cryptography offers some of the most attractive primitives believed to be resistant to quantum computers. Following increasing interest from both companies and government agencies in building quantum computers, a number of works have proposed instantiations of practical post-quantum key exchange protocols based on hard problems in ideal lattices, mainly based on the Ring Learning With Errors (R-LWE) problem. While ideal lattices facilitate major efficiency and storage benefits over their non-ideal counterparts, the additional ring structure that enables these advantages also raises concerns about the assumed difficulty of the underlying problems. Thus, a question of significant interest to cryptographers, and especially to those currently placing bets on primitives that will withstand quantum adversaries, is how much of an advantage the additional ring structure actually gives in practice. Despite conventional wisdom that generic lattices might be too slow and unwieldy, we demonstrate that LWE-based key exchange is quite practical: our constant time implementation requires around 1.3ms computation time for each party; compared to the recent NewHope R-LWE scheme, communication sizes increase by a factor of 4.7x, but remain under 12 KiB in each direction. Our protocol is competitive when used for serving web pages over TLS; when partnered with ECDSA signatures, latencies increase by less than a factor of 1.6x, and (even under heavy load) server throughput only decreases by factors of 1.5x and 1.2x when serving typical 1 KiB and 100 KiB pages, respectively. To achieve these practical results, our protocol takes advantage of several innovations. These include techniques to optimize communication bandwidth, dynamic generation of public parameters (which also offers additional security against backdoors), carefully chosen error distributions, and tight security parameters.

  • Open Access English
    Authors: 
    Dammers, E.; Palm, M.; Damme, M. van; Vigouroux, C.; Smale, D.; Conway, S.; Toon, G.C.; Jones, N.; Nussbaumer, E.; Warneke, T.; +17 more
    Publisher: Copernicus GmbH
    Countries: Belgium, France, Netherlands, France
    Project: NSERC , ARC | Tropospheric ozone and ai... (DP110101948), ARC | High resolution Fourier t... (LE0668470)

    Global distributions of atmospheric ammonia (NH3) measured with satellite instruments such as the Infrared Atmospheric Sounding Interferometer (IASI) contain valuable information on NH3 concentrations and variability in regions not yet covered by ground-based instruments. Due to their large spatial coverage and (bi-)daily overpasses, the satellite observations have the potential to increase our knowledge of the distribution of NH3 emissions and associated seasonal cycles. However the observations remain poorly validated, with only a handful of available studies often using only surface measurements without any vertical information. In this study, we present the first validation of the IASI-NH3 product using ground-based Fourier transform infrared spectroscopy (FTIR) observations. Using a recently developed consistent retrieval strategy, NH3 concentration profiles have been retrieved using observations from nine Network for the Detection of Atmospheric Composition Change (NDACC) stations around the world between 2008 and 2015. We demonstrate the importance of strict spatio-temporal collocation criteria for the comparison. Large differences in the regression results are observed for changing intervals of spatial criteria, mostly due to terrain characteristics and the short lifetime of NH3 in the atmosphere. The seasonal variations of both datasets are consistent for most sites. Correlations are found to be high at sites in areas with considerable NH3 levels, whereas correlations are lower at sites with low atmospheric NH3 levels close to the detection limit of the IASI instrument. A combination of the observations from all sites (Nobs Combining double low line 547) give a mean relative difference of ĝ'32.4ĝ€±ĝ€(56.3)ĝ€%, a correlation r of 0.8 with a slope of 0.73. These results give an improved estimate of the IASI-NH3 product performance compared to the previous upper-bound estimates (-50 to +100%).

  • Open Access
    Authors: 
    Mackey, S.; Allgaier, N.; Chaarani, B.; Spechler, P.; Orr, C.; Bunn, J.; Allen, N.B.; Alia-Klein, N.; Batalla, A.; Blaine, S.; +51 more
    Publisher: American Psychiatric Association Publishing
    Countries: Netherlands, United States, Australia
    Project: NIH | Cerebral Correlates of Ea... (5R01AA021449-03), NIH | UCLA Training Program in ... (5T32DA024635-04), NIH | STIMULANT DEPENDENCE: NEU... (1R01DA018307-01), NIH | Thalamic cortical dysfunc... (5K25DA040032-04), NIH | The Role of Executive Fun... (3R01DA014100-01S1), NHMRC | Enhancing and integrating... (1117188), NIH | Human Subjects Core: Prot... (5PL1DA024859-02), NHMRC | Quantifying the neurocogn... (459111), ARC | Cannabis and the brain: t... (FT110100752), NIH | Cognitive control and coc... (2R01DA023248-06A1),...

    Contains fulltext : 200963.pdf (Publisher’s version ) (Closed access) Objective: Although lower brain volume has been routinely observed in individuals with substance dependence compared with nondependent control subjects, the brain regions exhibiting lower volume have not been consistent across studies. In addition, it is not clear whether a common set of regions are involved in substance dependence regardless of the substance used or whether some brain volume effects are substance specific. Resolution of these issues may contribute to the identification of clinically relevant imaging biomarkers. Using pooled data from 14 countries, the authors sought to identify general and substance-specific associations between dependence and regional brain volumes. Method: Brain structure was examined in a mega-analysis of previously published data pooled from 23 laboratories, including 3,240 individuals, 2,140 of whom had substance dependence on one of five substances: alcohol, nicotine, cocaine, methamphetamine, or cannabis. Subcortical volume and cortical thickness in regions defined by FreeSurfer were compared with nondependent control subjects when all sampled substance categories were combined, as well as separately, while controlling for age, sex, imaging site, and total intracranial volume. Because of extensive associations with alcohol dependence, a secondary contrast was also performed for dependence on all substances except alcohol. An optimized split-half strategy was used to assess the reliability of the findings. Results: Lower volume or thickness was observed in many brain regions in individuals with substance dependence. The greatest effects were associated with alcohol use disorder. A set of affected regions related to dependence in general, regardless of the substance, included the insula and the medial orbitofrontal cortex. Furthermore, a support vector machine multivariate classification of regional brain volumes successfully classified individuals with substance dependence on alcohol or nicotine relative to nondependent control subjects. Conclusions: The results indicate that dependence on a range of different substances shares a common neural substrate and that differential patterns of regional volume could serve as useful biomarkers of dependence on alcohol and nicotine. 10 p.

  • Open Access
    Authors: 
    Arjan B. te Pas; Marcus J. Kitchen; Katie Lee; Megan J. Wallace; Andreas Fouras; Robert A. Lewis; Naoto Yagi; Kentaro Uesugi; Stuart B. Hooper;
    Publisher: Springer Science and Business Media LLC
    Country: Netherlands
    Project: ARC | Low dose methods for dete... (DP110101941), NIH | Facilitating The Physiolo... (1R01HD072848-01A1)

    Background: A sustained inflation (SI) facilitates lung aeration, but the most effective pressure and duration are unknown. We investigated the effect of gestational age (GA) and airway liquid volume on the required inflation pressure and SI duration. Methods: Rabbit kittens were delivered at 27, 29, and 30 d gestation, intubated and airway liquid was aspirated. Either no liquid (control) or 30 ml/kg of liquid was returned to the airways. Lung gas volumes were measured by plethysmography and phase-contrast X-ray-imaging. Starting at 22 cmH2O, airway pressure was increased until airflow commenced and pressure was then held constant. The SI was truncated when 20 ml/kg air had entered the lung and ventilation continued with intermittent positive pressure ventilation (iPPV). Results: Higher SI pressures and longer durations were required in 27-d kittens compared to 30-d kittens. During iPPV, 27-d kittens needed higher pressures and had lower functional residual capacity (FRC) compared to 30-d kittens. Adding lung liquid increased SI duration, reduced FRC, and increased resistance and pressures during iPPV in 29- and 30-d kittens. Conclusion: Immature kittens required higher starting pressures and longer SI durations to achieve a set inflation volume. Larger airway liquid volumes adversely affected lung function during iPPV in older but not young kittens.

  • Open Access English
    Authors: 
    MacDonald, K.;
    Country: Netherlands
    Project: NSF | Collaborative Research: I... (0725126), NSF | Collaborative research: I... (0725219), NSF | Testing models of ancient... (1725123), NSF | New Stratigraphic and Arc... (0852292), NSF | U.S.-Kenya IRES: Origins ... (1358200), NSF | Collaborative Research: I... (0725136), NSF | Long Term Human Response ... (1523986), NSF | Collaborative research: I... (0725122), EC | ORACEAF (283366), NSF | Collaborative research: I... (0725147),...

    There is no consensus on the chronology of fire use, with suggestions ranging from earliest use by Homo erectus 1.8 mya to relatively recent Anatomically Modern Humans. While it is widely agreed that fire would have been of great assistance in moving into areas with a temperate climate, early sites from middle latitudes across Eurasia lack convincing evidence for fire use before about 400,000 years ago. It is not clear whether this represents a real pattern, or a limitation to past research methods and survival. Establishing a firm chronology for the use of fire requires refined interpretation of fire residues at early sites. An alternative approach, taking the pattern (provisionally) as real, is to investigate how hominins could have solved important survival problems at middle latitudes without using fire. This article addresses strategies for thermoregulation in the absence of fire in conditions experienced by hominins in north-west Europe before 400,000 years ago. Four main hypotheses are proposed, involving strategies based primarily on 1) winter fur and subcutaneous fat, 2) hibernation, 3) enhanced heat production, and 4) a combination of cultural insulation particularly clothing and insulative baby carriers with enhanced heat production. Given the trade-offs of these strategies, I will consider their plausibility for the early occupants of Europe, and discuss how the most plausible strategies could be detected in future research.

  • Open Access English
    Authors: 
    Wolff, Jonci N.; Pichaud, Nicolas; Camus, Maria F.; Côté, Geneviève; Blier, Pierre U.; Dowling, Damian K.;
    Publisher: Dryad
    Project: NSERC , ARC | Sexual conflict in the mi... (DP1092897)

    The ancient acquisition of the mitochondrion into the ancestor of modern-day eukaryotes is thought to have been pivotal in facilitating the evolution of complex life. Mitochondria retain their own diminutive genome, with mitochondrial genes encoding core subunits involved in oxidative phosphorylation. Traditionally, it was assumed that there was little scope for genetic variation to accumulate and be maintained within the mitochondrial genome. However, in the past decade, mitochondrial genetic variation has been routinely tied to the expression of life-history traits such as fertility, development and longevity. To examine whether these broad-scale effects on life-history trait expression might ultimately find their root in mitochondrially mediated effects on core bioenergetic function, we measured the effects of genetic variation across twelve different mitochondrial haplotypes on respiratory capacity and mitochondrial quantity in the fruit fly, Drosophila melanogaster. We used strains of flies that differed only in their mitochondrial haplotype, and tested each sex separately at two different adult ages. Mitochondrial haplotypes affected both respiratory capacity and mitochondrial quantity. However, these effects were highly context-dependent, with the genetic effects contingent on both the sex and the age of the flies. These sex- and age-specific genetic effects are likely to resonate across the entire organismal life-history, providing insights into how mitochondrial genetic variation may contribute to sex-specific trajectories of life-history evolution. Alstonville_DryadBarcelona_DryadBrownsville_DryadDahomey_DryadHawaii_DryadIsrael_DryadJapan_DryadMadang_DryadMysore_DryadOregon_DryadPuerto Montt_DryadSweden_Dryad

  • Open Access
    Authors: 
    Lee, R.G.; Balasubramaniam, S.; Stentenbach, M.; Kralj, T.; McCubbin, T.; Padman, B.; Smith, J.; Riley, L.G.; Priyadarshi, A.; Peng, L.Y.; +22 more
    Publisher: Oxford University Press (OUP)
    Country: Netherlands
    Project: ARC | Discovery Projects - Gran... (DP180101656), NHMRC | Preparing Australia for G... (GNT1113531), NHMRC | Minimising the impact of ... (GNT1155244), NHMRC | Regulation of mitochondri... (GNT1058442), ARC | Discovery Projects - Gran... (DP190102464)

    Abstract Mitochondrial diseases are a group of inherited diseases with highly varied and complex clinical presentations. Here, we report four individuals, including two siblings, affected by a progressive mitochondrial encephalopathy with biallelic variants in the cardiolipin biosynthesis gene CRLS1. Three affected individuals had a similar infantile presentation comprising progressive encephalopathy, bull’s eye maculopathy, auditory neuropathy, diabetes insipidus, autonomic instability, cardiac defects and early death. The fourth affected individual presented with chronic encephalopathy with neurodevelopmental regression, congenital nystagmus with decreased vision, sensorineural hearing loss, failure to thrive and acquired microcephaly. Using patient-derived fibroblasts, we characterized cardiolipin synthase 1 (CRLS1) dysfunction that impaired mitochondrial morphology and biogenesis, providing functional evidence that the CRLS1 variants cause mitochondrial disease. Lipid profiling in fibroblasts from two patients further confirmed the functional defect demonstrating reduced cardiolipin levels, altered acyl-chain composition and significantly increased levels of phosphatidylglycerol, the substrate of CRLS1. Proteomic profiling of patient cells and mouse Crls1 knockout cell lines identified both endoplasmic reticular and mitochondrial stress responses, and key features that distinguish between varying degrees of cardiolipin insufficiency. These findings support that deleterious variants in CRLS1 cause an autosomal recessive mitochondrial disease, presenting as a severe encephalopathy with multi-systemic involvement. Furthermore, we identify key signatures in cardiolipin and proteome profiles across various degrees of cardiolipin loss, facilitating the use of omics technologies to guide future diagnosis of mitochondrial diseases.

  • Publication . Article . Other literature type . 2016
    Open Access
    Authors: 
    Momoko Horikoshi; Robin N Beaumont; Felix R. Day; Nicole M. Warrington; Marjolein N. Kooijman; Juan Fernández-Tajes; Bjarke Feenstra; Natalie R. van Zuydam; Kyle J. Gaulton; Niels Grarup; +153 more
    Publisher: Springer Science and Business Media LLC
    Countries: United Kingdom, United Kingdom, Australia, United Kingdom, Netherlands, Germany, United Kingdom, United Kingdom
    Project: NIH | Prospective meta-analyses... (1R01HL103612-01A1), NIH | HYPERGLYCEMIA AND ADVERSE... (1R01HD034243-01A2), AKA | The Cardiovascular Risk i... (121584), UKRI | Identifying non-coding mu... (MR/M005070/1), NIH | Type 1 Diabetes Genetics ... (1U01DK062418-01), NIH | Genome Wide Association C... (5U01HG004446-04), UKRI | Genetic and transcription... (MR/K011480/1), WT | Using genetics to underst... (104150), AKA | Role of early life risk f... (124282), NIH | COMMUNITY AND COHORT SURV... (N01HC055016-002),...

    Birth weight (BW) has been shown to be influenced by both fetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease. These life-course associations have often been attributed to the impact of an adverse early life environment. Here, we performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where fetal genotype was associated with BW (P < 5 × 10(-8)). Overall, approximately 15% of variance in BW was captured by assays of fetal genetic variation. Using genetic association alone, we found strong inverse genetic correlations between BW and systolic blood pressure (Rg = -0.22, P = 5.5 × 10(-13)), T2D (Rg = -0.27, P = 1.1 × 10(-6)) and coronary artery disease (Rg = -0.30, P = 6.5 × 10(-9)). In addition, using large -cohort datasets, we demonstrated that genetic factors were the major contributor to the negative covariance between BW and future cardiometabolic risk. Pathway analyses indicated that the protein products of genes within BW-associated regions were enriched for diverse processes including insulin signalling, glucose homeostasis, glycogen biosynthesis and chromatin remodelling. There was also enrichment of associations with BW in known imprinted regions (P = 1.9 × 10(-4)). We demonstrate that life-course associations between early growth phenotypes and adult cardiometabolic disease are in part the result of shared genetic effects and identify some of the pathways through which these causal genetic effects are mediated.

  • Open Access
    Authors: 
    Jessica R. Crawshaw; Stuart B. Hooper; Arjan B. te Pas; Beth J. Allison; Megan J. Wallace; Lauren Kerr; Robert A. Lewis; Colin J Morley; A. F. T. Leong; Marcus J. Kitchen;
    Publisher: American Physiological Society
    Country: Netherlands
    Project: ARC | Low dose methods for dete... (DP110101941), NHMRC | Macrophage activation (436608), NHMRC | Phase contrast X-ray imag... (491103), ARC | Phase Contrast X-ray Imag... (DP0664664)

    Antenatal glucocorticoids, exogenous surfactant, and positive end-expiratory pressure (PEEP) ventilation are commonly provided to preterm infants to enhance respiratory function after birth. It is unclear how these treatments interact to improve the transition to air-breathing at birth. We investigated the relative contribution of antenatal betamethasone, prophylactic surfactant, and PEEP (3 cmH2O) on functional residual capacity (FRC) and dynamic lung compliance (CDL) in preterm (28 day GA) rabbit kittens at birth. Kittens were delivered by cesarean section and mechanically ventilated. FRC was calculated from X-ray images, and CDL was measured using plethysmography. Without betamethasone, PEEP increased FRC recruitment and CDL. Surfactant did not further increase FRC, but significantly increased CDL. Betamethasone abolished the benefit of PEEP on FRC, but surfactant counteracted this effect of betamethasone. These findings indicate that low PEEP levels are insufficient to establish FRC at birth following betamethasone treatment. However, surfactant reversed the effect of betamethasone and when combined, these two treatments enhanced FRC recruitment irrespective of PEEP level.

  • Open Access
    Authors: 
    Kevin V. Croxall; J. D. Smith; Eric W. Pellegrini; Brent Groves; Alberto D. Bolatto; Rodrigo Herrera-Camus; Karin Sandstrom; Bruce T. Draine; Mark G. Wolfire; Lee Armus; +10 more
    Publisher: American Astronomical Society
    Countries: Netherlands, Italy, United Kingdom, United States, United Kingdom
    Project: ARC | ARC Future Fellowships - ... (FT140101202)

    The [C ii] 158 μm fine-structure line is the brightest emission line observed in local star-forming galaxies. As a major coolant of the gas-phase interstellar medium, [C ii] balances the heating, including that due to far-ultraviolet photons, which heat the gas via the photoelectric effect. However, the origin of [C ii] emission remains unclear because C+ can be found in multiple phases of the interstellar medium. Here we measure the fractions of [C ii] emission originating in the ionized and neutral gas phases of a sample of nearby galaxies. We use the [N ii] 205 μm fine-structure line to trace the ionized medium, thereby eliminating the strong density dependence that exists in the ratio of [C ii]/[N ii] 122 μm. Using the FIR [C ii] and [N ii] emission detected by the KINGFISH (Key Insights on Nearby Galaxies: a Far- Infrared Survey with Herschel) and Beyond the Peak Herschel programs, we show that 60%-80% of [C ii] emission originates from neutral gas. We find that the fraction of [C ii] originating in the neutral medium has a weak dependence on dust temperature and the surface density of star formation, and has a stronger dependence on the gas-phase metallicity. In metal-rich environments, the relatively cooler ionized gas makes substantially larger contributions to total [C ii] emission than at low abundance, contrary to prior expectations. Approximate calibrations of this metallicity trend are provided.

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Include:
The following results are related to Canada. Are you interested to view more results? Visit OpenAIRE - Explore.
52 Research products, page 1 of 6
  • Publication . Conference object . 2016
    Open Access
    Authors: 
    Joppe W. Bos; Craig Costello; Léo Ducas; Ilya Mironov; Michael Naehrig; Valeria Nikolaenko; Ananth Raghunathan; Douglas Stebila;
    Publisher: ACM
    Country: Netherlands
    Project: NSERC , ARC | Internet authentication p... (DP130104304), EC | PQCRYPTO (645622)

    Lattice-based cryptography offers some of the most attractive primitives believed to be resistant to quantum computers. Following increasing interest from both companies and government agencies in building quantum computers, a number of works have proposed instantiations of practical post-quantum key exchange protocols based on hard problems in ideal lattices, mainly based on the Ring Learning With Errors (R-LWE) problem. While ideal lattices facilitate major efficiency and storage benefits over their non-ideal counterparts, the additional ring structure that enables these advantages also raises concerns about the assumed difficulty of the underlying problems. Thus, a question of significant interest to cryptographers, and especially to those currently placing bets on primitives that will withstand quantum adversaries, is how much of an advantage the additional ring structure actually gives in practice. Despite conventional wisdom that generic lattices might be too slow and unwieldy, we demonstrate that LWE-based key exchange is quite practical: our constant time implementation requires around 1.3ms computation time for each party; compared to the recent NewHope R-LWE scheme, communication sizes increase by a factor of 4.7x, but remain under 12 KiB in each direction. Our protocol is competitive when used for serving web pages over TLS; when partnered with ECDSA signatures, latencies increase by less than a factor of 1.6x, and (even under heavy load) server throughput only decreases by factors of 1.5x and 1.2x when serving typical 1 KiB and 100 KiB pages, respectively. To achieve these practical results, our protocol takes advantage of several innovations. These include techniques to optimize communication bandwidth, dynamic generation of public parameters (which also offers additional security against backdoors), carefully chosen error distributions, and tight security parameters.

  • Open Access English
    Authors: 
    Dammers, E.; Palm, M.; Damme, M. van; Vigouroux, C.; Smale, D.; Conway, S.; Toon, G.C.; Jones, N.; Nussbaumer, E.; Warneke, T.; +17 more
    Publisher: Copernicus GmbH
    Countries: Belgium, France, Netherlands, France
    Project: NSERC , ARC | Tropospheric ozone and ai... (DP110101948), ARC | High resolution Fourier t... (LE0668470)

    Global distributions of atmospheric ammonia (NH3) measured with satellite instruments such as the Infrared Atmospheric Sounding Interferometer (IASI) contain valuable information on NH3 concentrations and variability in regions not yet covered by ground-based instruments. Due to their large spatial coverage and (bi-)daily overpasses, the satellite observations have the potential to increase our knowledge of the distribution of NH3 emissions and associated seasonal cycles. However the observations remain poorly validated, with only a handful of available studies often using only surface measurements without any vertical information. In this study, we present the first validation of the IASI-NH3 product using ground-based Fourier transform infrared spectroscopy (FTIR) observations. Using a recently developed consistent retrieval strategy, NH3 concentration profiles have been retrieved using observations from nine Network for the Detection of Atmospheric Composition Change (NDACC) stations around the world between 2008 and 2015. We demonstrate the importance of strict spatio-temporal collocation criteria for the comparison. Large differences in the regression results are observed for changing intervals of spatial criteria, mostly due to terrain characteristics and the short lifetime of NH3 in the atmosphere. The seasonal variations of both datasets are consistent for most sites. Correlations are found to be high at sites in areas with considerable NH3 levels, whereas correlations are lower at sites with low atmospheric NH3 levels close to the detection limit of the IASI instrument. A combination of the observations from all sites (Nobs Combining double low line 547) give a mean relative difference of ĝ'32.4ĝ€±ĝ€(56.3)ĝ€%, a correlation r of 0.8 with a slope of 0.73. These results give an improved estimate of the IASI-NH3 product performance compared to the previous upper-bound estimates (-50 to +100%).

  • Open Access
    Authors: 
    Mackey, S.; Allgaier, N.; Chaarani, B.; Spechler, P.; Orr, C.; Bunn, J.; Allen, N.B.; Alia-Klein, N.; Batalla, A.; Blaine, S.; +51 more
    Publisher: American Psychiatric Association Publishing
    Countries: Netherlands, United States, Australia
    Project: NIH | Cerebral Correlates of Ea... (5R01AA021449-03), NIH | UCLA Training Program in ... (5T32DA024635-04), NIH | STIMULANT DEPENDENCE: NEU... (1R01DA018307-01), NIH | Thalamic cortical dysfunc... (5K25DA040032-04), NIH | The Role of Executive Fun... (3R01DA014100-01S1), NHMRC | Enhancing and integrating... (1117188), NIH | Human Subjects Core: Prot... (5PL1DA024859-02), NHMRC | Quantifying the neurocogn... (459111), ARC | Cannabis and the brain: t... (FT110100752), NIH | Cognitive control and coc... (2R01DA023248-06A1),...

    Contains fulltext : 200963.pdf (Publisher’s version ) (Closed access) Objective: Although lower brain volume has been routinely observed in individuals with substance dependence compared with nondependent control subjects, the brain regions exhibiting lower volume have not been consistent across studies. In addition, it is not clear whether a common set of regions are involved in substance dependence regardless of the substance used or whether some brain volume effects are substance specific. Resolution of these issues may contribute to the identification of clinically relevant imaging biomarkers. Using pooled data from 14 countries, the authors sought to identify general and substance-specific associations between dependence and regional brain volumes. Method: Brain structure was examined in a mega-analysis of previously published data pooled from 23 laboratories, including 3,240 individuals, 2,140 of whom had substance dependence on one of five substances: alcohol, nicotine, cocaine, methamphetamine, or cannabis. Subcortical volume and cortical thickness in regions defined by FreeSurfer were compared with nondependent control subjects when all sampled substance categories were combined, as well as separately, while controlling for age, sex, imaging site, and total intracranial volume. Because of extensive associations with alcohol dependence, a secondary contrast was also performed for dependence on all substances except alcohol. An optimized split-half strategy was used to assess the reliability of the findings. Results: Lower volume or thickness was observed in many brain regions in individuals with substance dependence. The greatest effects were associated with alcohol use disorder. A set of affected regions related to dependence in general, regardless of the substance, included the insula and the medial orbitofrontal cortex. Furthermore, a support vector machine multivariate classification of regional brain volumes successfully classified individuals with substance dependence on alcohol or nicotine relative to nondependent control subjects. Conclusions: The results indicate that dependence on a range of different substances shares a common neural substrate and that differential patterns of regional volume could serve as useful biomarkers of dependence on alcohol and nicotine. 10 p.

  • Open Access
    Authors: 
    Arjan B. te Pas; Marcus J. Kitchen; Katie Lee; Megan J. Wallace; Andreas Fouras; Robert A. Lewis; Naoto Yagi; Kentaro Uesugi; Stuart B. Hooper;
    Publisher: Springer Science and Business Media LLC
    Country: Netherlands
    Project: ARC | Low dose methods for dete... (DP110101941), NIH | Facilitating The Physiolo... (1R01HD072848-01A1)

    Background: A sustained inflation (SI) facilitates lung aeration, but the most effective pressure and duration are unknown. We investigated the effect of gestational age (GA) and airway liquid volume on the required inflation pressure and SI duration. Methods: Rabbit kittens were delivered at 27, 29, and 30 d gestation, intubated and airway liquid was aspirated. Either no liquid (control) or 30 ml/kg of liquid was returned to the airways. Lung gas volumes were measured by plethysmography and phase-contrast X-ray-imaging. Starting at 22 cmH2O, airway pressure was increased until airflow commenced and pressure was then held constant. The SI was truncated when 20 ml/kg air had entered the lung and ventilation continued with intermittent positive pressure ventilation (iPPV). Results: Higher SI pressures and longer durations were required in 27-d kittens compared to 30-d kittens. During iPPV, 27-d kittens needed higher pressures and had lower functional residual capacity (FRC) compared to 30-d kittens. Adding lung liquid increased SI duration, reduced FRC, and increased resistance and pressures during iPPV in 29- and 30-d kittens. Conclusion: Immature kittens required higher starting pressures and longer SI durations to achieve a set inflation volume. Larger airway liquid volumes adversely affected lung function during iPPV in older but not young kittens.

  • Open Access English
    Authors: 
    MacDonald, K.;
    Country: Netherlands
    Project: NSF | Collaborative Research: I... (0725126), NSF | Collaborative research: I... (0725219), NSF | Testing models of ancient... (1725123), NSF | New Stratigraphic and Arc... (0852292), NSF | U.S.-Kenya IRES: Origins ... (1358200), NSF | Collaborative Research: I... (0725136), NSF | Long Term Human Response ... (1523986), NSF | Collaborative research: I... (0725122), EC | ORACEAF (283366), NSF | Collaborative research: I... (0725147),...

    There is no consensus on the chronology of fire use, with suggestions ranging from earliest use by Homo erectus 1.8 mya to relatively recent Anatomically Modern Humans. While it is widely agreed that fire would have been of great assistance in moving into areas with a temperate climate, early sites from middle latitudes across Eurasia lack convincing evidence for fire use before about 400,000 years ago. It is not clear whether this represents a real pattern, or a limitation to past research methods and survival. Establishing a firm chronology for the use of fire requires refined interpretation of fire residues at early sites. An alternative approach, taking the pattern (provisionally) as real, is to investigate how hominins could have solved important survival problems at middle latitudes without using fire. This article addresses strategies for thermoregulation in the absence of fire in conditions experienced by hominins in north-west Europe before 400,000 years ago. Four main hypotheses are proposed, involving strategies based primarily on 1) winter fur and subcutaneous fat, 2) hibernation, 3) enhanced heat production, and 4) a combination of cultural insulation particularly clothing and insulative baby carriers with enhanced heat production. Given the trade-offs of these strategies, I will consider their plausibility for the early occupants of Europe, and discuss how the most plausible strategies could be detected in future research.

  • Open Access English
    Authors: 
    Wolff, Jonci N.; Pichaud, Nicolas; Camus, Maria F.; Côté, Geneviève; Blier, Pierre U.; Dowling, Damian K.;
    Publisher: Dryad
    Project: NSERC , ARC | Sexual conflict in the mi... (DP1092897)

    The ancient acquisition of the mitochondrion into the ancestor of modern-day eukaryotes is thought to have been pivotal in facilitating the evolution of complex life. Mitochondria retain their own diminutive genome, with mitochondrial genes encoding core subunits involved in oxidative phosphorylation. Traditionally, it was assumed that there was little scope for genetic variation to accumulate and be maintained within the mitochondrial genome. However, in the past decade, mitochondrial genetic variation has been routinely tied to the expression of life-history traits such as fertility, development and longevity. To examine whether these broad-scale effects on life-history trait expression might ultimately find their root in mitochondrially mediated effects on core bioenergetic function, we measured the effects of genetic variation across twelve different mitochondrial haplotypes on respiratory capacity and mitochondrial quantity in the fruit fly, Drosophila melanogaster. We used strains of flies that differed only in their mitochondrial haplotype, and tested each sex separately at two different adult ages. Mitochondrial haplotypes affected both respiratory capacity and mitochondrial quantity. However, these effects were highly context-dependent, with the genetic effects contingent on both the sex and the age of the flies. These sex- and age-specific genetic effects are likely to resonate across the entire organismal life-history, providing insights into how mitochondrial genetic variation may contribute to sex-specific trajectories of life-history evolution. Alstonville_DryadBarcelona_DryadBrownsville_DryadDahomey_DryadHawaii_DryadIsrael_DryadJapan_DryadMadang_DryadMysore_DryadOregon_DryadPuerto Montt_DryadSweden_Dryad

  • Open Access
    Authors: 
    Lee, R.G.; Balasubramaniam, S.; Stentenbach, M.; Kralj, T.; McCubbin, T.; Padman, B.; Smith, J.; Riley, L.G.; Priyadarshi, A.; Peng, L.Y.; +22 more
    Publisher: Oxford University Press (OUP)
    Country: Netherlands
    Project: ARC | Discovery Projects - Gran... (DP180101656), NHMRC | Preparing Australia for G... (GNT1113531), NHMRC | Minimising the impact of ... (GNT1155244), NHMRC | Regulation of mitochondri... (GNT1058442), ARC | Discovery Projects - Gran... (DP190102464)

    Abstract Mitochondrial diseases are a group of inherited diseases with highly varied and complex clinical presentations. Here, we report four individuals, including two siblings, affected by a progressive mitochondrial encephalopathy with biallelic variants in the cardiolipin biosynthesis gene CRLS1. Three affected individuals had a similar infantile presentation comprising progressive encephalopathy, bull’s eye maculopathy, auditory neuropathy, diabetes insipidus, autonomic instability, cardiac defects and early death. The fourth affected individual presented with chronic encephalopathy with neurodevelopmental regression, congenital nystagmus with decreased vision, sensorineural hearing loss, failure to thrive and acquired microcephaly. Using patient-derived fibroblasts, we characterized cardiolipin synthase 1 (CRLS1) dysfunction that impaired mitochondrial morphology and biogenesis, providing functional evidence that the CRLS1 variants cause mitochondrial disease. Lipid profiling in fibroblasts from two patients further confirmed the functional defect demonstrating reduced cardiolipin levels, altered acyl-chain composition and significantly increased levels of phosphatidylglycerol, the substrate of CRLS1. Proteomic profiling of patient cells and mouse Crls1 knockout cell lines identified both endoplasmic reticular and mitochondrial stress responses, and key features that distinguish between varying degrees of cardiolipin insufficiency. These findings support that deleterious variants in CRLS1 cause an autosomal recessive mitochondrial disease, presenting as a severe encephalopathy with multi-systemic involvement. Furthermore, we identify key signatures in cardiolipin and proteome profiles across various degrees of cardiolipin loss, facilitating the use of omics technologies to guide future diagnosis of mitochondrial diseases.

  • Publication . Article . Other literature type . 2016
    Open Access
    Authors: 
    Momoko Horikoshi; Robin N Beaumont; Felix R. Day; Nicole M. Warrington; Marjolein N. Kooijman; Juan Fernández-Tajes; Bjarke Feenstra; Natalie R. van Zuydam; Kyle J. Gaulton; Niels Grarup; +153 more
    Publisher: Springer Science and Business Media LLC
    Countries: United Kingdom, United Kingdom, Australia, United Kingdom, Netherlands, Germany, United Kingdom, United Kingdom
    Project: NIH | Prospective meta-analyses... (1R01HL103612-01A1), NIH | HYPERGLYCEMIA AND ADVERSE... (1R01HD034243-01A2), AKA | The Cardiovascular Risk i... (121584), UKRI | Identifying non-coding mu... (MR/M005070/1), NIH | Type 1 Diabetes Genetics ... (1U01DK062418-01), NIH | Genome Wide Association C... (5U01HG004446-04), UKRI | Genetic and transcription... (MR/K011480/1), WT | Using genetics to underst... (104150), AKA | Role of early life risk f... (124282), NIH | COMMUNITY AND COHORT SURV... (N01HC055016-002),...

    Birth weight (BW) has been shown to be influenced by both fetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease. These life-course associations have often been attributed to the impact of an adverse early life environment. Here, we performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where fetal genotype was associated with BW (P < 5 × 10(-8)). Overall, approximately 15% of variance in BW was captured by assays of fetal genetic variation. Using genetic association alone, we found strong inverse genetic correlations between BW and systolic blood pressure (Rg = -0.22, P = 5.5 × 10(-13)), T2D (Rg = -0.27, P = 1.1 × 10(-6)) and coronary artery disease (Rg = -0.30, P = 6.5 × 10(-9)). In addition, using large -cohort datasets, we demonstrated that genetic factors were the major contributor to the negative covariance between BW and future cardiometabolic risk. Pathway analyses indicated that the protein products of genes within BW-associated regions were enriched for diverse processes including insulin signalling, glucose homeostasis, glycogen biosynthesis and chromatin remodelling. There was also enrichment of associations with BW in known imprinted regions (P = 1.9 × 10(-4)). We demonstrate that life-course associations between early growth phenotypes and adult cardiometabolic disease are in part the result of shared genetic effects and identify some of the pathways through which these causal genetic effects are mediated.

  • Open Access
    Authors: 
    Jessica R. Crawshaw; Stuart B. Hooper; Arjan B. te Pas; Beth J. Allison; Megan J. Wallace; Lauren Kerr; Robert A. Lewis; Colin J Morley; A. F. T. Leong; Marcus J. Kitchen;
    Publisher: American Physiological Society
    Country: Netherlands
    Project: ARC | Low dose methods for dete... (DP110101941), NHMRC | Macrophage activation (436608), NHMRC | Phase contrast X-ray imag... (491103), ARC | Phase Contrast X-ray Imag... (DP0664664)

    Antenatal glucocorticoids, exogenous surfactant, and positive end-expiratory pressure (PEEP) ventilation are commonly provided to preterm infants to enhance respiratory function after birth. It is unclear how these treatments interact to improve the transition to air-breathing at birth. We investigated the relative contribution of antenatal betamethasone, prophylactic surfactant, and PEEP (3 cmH2O) on functional residual capacity (FRC) and dynamic lung compliance (CDL) in preterm (28 day GA) rabbit kittens at birth. Kittens were delivered by cesarean section and mechanically ventilated. FRC was calculated from X-ray images, and CDL was measured using plethysmography. Without betamethasone, PEEP increased FRC recruitment and CDL. Surfactant did not further increase FRC, but significantly increased CDL. Betamethasone abolished the benefit of PEEP on FRC, but surfactant counteracted this effect of betamethasone. These findings indicate that low PEEP levels are insufficient to establish FRC at birth following betamethasone treatment. However, surfactant reversed the effect of betamethasone and when combined, these two treatments enhanced FRC recruitment irrespective of PEEP level.

  • Open Access
    Authors: 
    Kevin V. Croxall; J. D. Smith; Eric W. Pellegrini; Brent Groves; Alberto D. Bolatto; Rodrigo Herrera-Camus; Karin Sandstrom; Bruce T. Draine; Mark G. Wolfire; Lee Armus; +10 more
    Publisher: American Astronomical Society
    Countries: Netherlands, Italy, United Kingdom, United States, United Kingdom
    Project: ARC | ARC Future Fellowships - ... (FT140101202)

    The [C ii] 158 μm fine-structure line is the brightest emission line observed in local star-forming galaxies. As a major coolant of the gas-phase interstellar medium, [C ii] balances the heating, including that due to far-ultraviolet photons, which heat the gas via the photoelectric effect. However, the origin of [C ii] emission remains unclear because C+ can be found in multiple phases of the interstellar medium. Here we measure the fractions of [C ii] emission originating in the ionized and neutral gas phases of a sample of nearby galaxies. We use the [N ii] 205 μm fine-structure line to trace the ionized medium, thereby eliminating the strong density dependence that exists in the ratio of [C ii]/[N ii] 122 μm. Using the FIR [C ii] and [N ii] emission detected by the KINGFISH (Key Insights on Nearby Galaxies: a Far- Infrared Survey with Herschel) and Beyond the Peak Herschel programs, we show that 60%-80% of [C ii] emission originates from neutral gas. We find that the fraction of [C ii] originating in the neutral medium has a weak dependence on dust temperature and the surface density of star formation, and has a stronger dependence on the gas-phase metallicity. In metal-rich environments, the relatively cooler ionized gas makes substantially larger contributions to total [C ii] emission than at low abundance, contrary to prior expectations. Approximate calibrations of this metallicity trend are provided.