166 research outputs found
Contributions of green infrastructure to enhancing urban resilience
Š 2018, The Author(s). After briefly reviewing key resilience engineering perspectives and summarising some green infrastructure (GI) tools, we present the contributions that GI can make to enhancing urban resilience and maintaining critical system functionality across complex integrated socialâecological and technical systems. We then examine five key challenges for the effective implementation of GI that include (1) standards; (2) regulation; (3) socio-economic factors; (4) financeability; and (5) innovation. We highlight ways in which these challenges are being dealt with around the world, particularly through the use of approaches that are both context appropriate and socially inclusive. Although progress surmounting these challenges has been made, more needs to be done to ensure that GI approaches are inclusive and appropriate and feature equally alongside more traditional âgreyâ infrastructure in the future of urban resilience planning. This research was undertaken for the Resilience Shift initiative to shift the approach to resilience in practice for critical infrastructure sectors. The programme aims to help practitioners involved in critical infrastructure to make decisions differently, contributing to a safer and better world
Visual perceptual load induces inattentional deafness
In this article, we establish a new phenomenon of âinattentional deafnessâ and highlight the level of load on visual attention as a critical determinant of this phenomenon. In three experiments, we modified an inattentional blindness paradigm to assess inattentional deafness. Participants made either a low- or high-load visual discrimination concerning a cross shape (respectively, a discrimination of line color or of line length with a subtle length difference). A brief pure tone was presented simultaneously with the visual task display on a final trial. Failures to notice the presence of this tone (i.e., inattentional deafness) reached a rate of 79% in the high-visual-load condition, significantly more than in the low-load condition. These findings establish the phenomenon of inattentional deafness under visual load, thereby extending the load theory of attention (e.g., Lavie, Journal of Experimental Psychology. Human Perception and Performance, 25, 596â616, 1995) to address the cross-modal effects of visual perceptual load
SINE RNA Induces Severe Developmental Defects in Arabidopsis thaliana and Interacts with HYL1 (DRB1), a Key Member of the DCL1 Complex
The proper temporal and spatial expression of genes during plant development is governed, in part, by the regulatory activities of various types of small RNAs produced by the different RNAi pathways. Here we report that transgenic Arabidopsis plants constitutively expressing the rapeseed SB1 SINE retroposon exhibit developmental defects resembling those observed in some RNAi mutants. We show that SB1 RNA interacts with HYL1 (DRB1), a double-stranded RNA-binding protein (dsRBP) that associates with the Dicer homologue DCL1 to produce microRNAs. RNase V1 protection assays mapped the binding site of HYL1 to a SB1 region that mimics the hairpin structure of microRNA precursors. We also show that HYL1, upon binding to RNA substrates, induces conformational changes that force single-stranded RNA regions to adopt a structured helix-like conformation. Xenopus laevis ADAR1, but not Arabidopsis DRB4, binds SB1 RNA in the same region as HYL1, suggesting that SINE RNAs bind only a subset of dsRBPs. Consistently, DCL4-DRB4-dependent miRNA accumulation was unchanged in SB1 transgenic Arabidopsis, whereas DCL1-HYL1-dependent miRNA and DCL1-HYL1-DCL4-DRB4-dependent tasiRNA accumulation was decreased. We propose that SINE RNA can modulate the activity of the RNAi pathways in plants and possibly in other eukaryotes
Interaction between genetic and epigenetic variation defines gene expression patterns at the asthma-associated locus 17q12-q21 in lymphoblastoid cell lines
Phenotypic variation results from variation in gene expression, which is modulated by genetic and/or epigenetic factors. To understand the molecular basis of human disease, interaction between genetic and epigenetic factors needs to be taken into account. The asthma-associated region 17q12-q21 harbors three genes, the zona pellucida binding protein 2 (ZPBP2), gasdermin B (GSDMB) and ORM1-like 3 (ORMDL3), that show allele-specific differences in expression levels in lymphoblastoid cell lines (LCLs) and CD4+ T cells. Here, we report a molecular dissection of allele-specific transcriptional regulation of the genes within the chromosomal region 17q12-q21 combining in vitro transfection, formaldehyde-assisted isolation of regulatory elements, chromatin immunoprecipitation and DNA methylation assays in LCLs. We found that a single nucleotide polymorphism rs4795397 influences the activity of ZPBP2 promoter in vitro in an allele-dependent fashion, and also leads to nucleosome repositioning on the asthma-associated allele. However, variable methylation of exon 1 of ZPBP2 masks the strong genetic effect on ZPBP2 promoter activity in LCLs. In contrast, the ORMDL3 promoter is fully unmethylated, which allows detection of genetic effects on its transcription. We conclude that the cis-regulatory effects on 17q12-q21 gene expression result from interaction between several regulatory polymorphisms and epigenetic factors within the cis-regulatory haplotype region
The TP53 Arg72Pro and MDM2 309G>T polymorphisms are not associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers
Background: The TP53 pathway, in which TP53 and its negative regulator MDM2 are the central elements, has an important role in carcinogenesis, particularly in BRCA1- and BRCA2-mediated carcinogenesis. A single nucleotide polymorphism (SNP) in the promoter region of MDM2 (309T>G, rs2279744) and a coding SNP of TP53 (Arg72Pro, rs1042522) have been shown to be of functional significance. Methods: To investigate whether these SNPs modify breast cancer risk for BRCA1 and BRCA2 mutation carriers, we pooled genotype data on the TP53 Arg72Pro SNP in 7011 mutation carriers and on the MDM2 309T>G SNP in 2222 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analysed using a Cox proportional hazards model within a retrospective likelihood framework. Results: No association was found between these SNPs and breast cancer risk for BRCA1 (TP53: per-allele hazard ratio (HR)=1.01, 95% confidence interval (CI): 0.93â1.10, Ptrend=0.77; MDM2: HR=0.96, 95%CI: 0.84â1.09, Ptrend=0.54) or for BRCA2 mutation carriers (TP53: HR=0.99, 95%CI: 0.87â1.12, Ptrend=0.83; MDM2: HR=0.98, 95%CI: 0.80â1.21, Ptrend=0.88). We also evaluated the potential combined effects of both SNPs on breast cancer risk, however, none of their combined genotypes showed any evidence of association. Conclusion: There was no evidence that TP53 Arg72Pro or MDM2 309T>G, either singly or in combination, influence breast cancer risk in BRCA1 or BRCA2 mutation carriers. O M Sinilnikova1,2, A C Antoniou3, J Simard4, S Healey5, M LĂŠonĂŠ1, D Sinnett6,7, A B Spurdle5, J Beesley5, X Chen5, kConFab8, M H Greene9, J T Loud9, F Lejbkowicz10, G Rennert10, S Dishon10, I L Andrulis11,12, OCGN11, S M Domchek13, K L Nathanson13, S Manoukian14, P Radice15,16, I Konstantopoulou17, I Blanco18, A L Laborde19, M DurĂĄn20, A Osorio21, J Benitez21, U Hamann22, F B L Hogervorst23, T A M van Os24, H J P Gille25, HEBON23, S Peock3, M Cook3, C Luccarini26, D G Evans27, F Lalloo27, R Eeles28, G Pichert29, R Davidson30, T Cole31, J Cook32, J Paterson33, C Brewer34, EMBRACE3, D J Hughes35, I Coupier36,37, S Giraud1, F Coulet38, C Colas38, F Soubrier38, E Rouleau39, I Bièche39, R Lidereau39, L Demange40, C Nogues40, H T Lynch41, GEMO1,2,42, R K Schmutzler43, B Versmold43, C Engel44, A Meindl45, N Arnold46, C Sutter47, H Deissler48, D Schaefer49, U G Froster50, GC-HBOC43,44,45,46,47,48,49,50, K Aittomäki51, H Nevanlinna52, L McGuffog3, D F Easton3, G Chenevix-Trench5 and D Stoppa-Lyonnet42 on behalf of the Consortium of Investigators of Modifiers of BRCA1/
Genetic architecture of gene expression in ovine skeletal muscle
In livestock populations the genetic contribution to muscling is intensively monitored in the progeny of industry sires and used as a tool in selective breeding programs. The genes and pathways conferring this genetic merit are largely undefined. Genetic variation within a population has potential, amongst other mechanisms, to alter gene expression via cis- or trans-acting mechanisms in a manner that impacts the functional activities of specific pathways that contribute to muscling traits. By integrating sire-based genetic merit information for a muscling trait with progeny-based gene expression data we directly tested the hypothesis that there is genetic structure in the gene expression program in ovine skeletal muscle.
Results
The genetic performance of six sires for a well defined muscling trait, longissimus lumborum muscle depth, was measured using extensive progeny testing and expressed as an Estimated Breeding Value by comparison with contemporary sires. Microarray gene expression data were obtained for longissimus lumborum samples taken from forty progeny of the six sires (4-8 progeny/sire). Initial unsupervised hierarchical clustering analysis revealed strong genetic architecture to the gene expression data, which also discriminated the sire-based Estimated Breeding Value for the trait. An integrated systems biology approach was then used to identify the major functional pathways contributing to the genetics of enhanced muscling by using both Estimated Breeding Value weighted gene co-expression network analysis and a differential gene co-expression network analysis. The modules of genes revealed by these analyses were enriched for a number of functional terms summarised as muscle sarcomere organisation and development, protein catabolism (proteosome), RNA processing, mitochondrial function and transcriptional regulation.
Conclusions
This study has revealed strong genetic structure in the gene expression program within ovine longissimus lumborum muscle. The balance between muscle protein synthesis, at the levels of both transcription and translation control, and protein catabolism mediated by regulated proteolysis is likely to be the primary determinant of the genetic merit for the muscling trait in this sheep population. There is also evidence that high genetic merit for muscling is associated with a fibre type shift toward fast glycolytic fibres. This study provides insight into mechanisms, presumably subject to strong artificial selection, that underpin enhanced muscling in sheep populations
Effect of Nitriding Voltage on the Impact Load Fatigue and Fracture Toughness Behaviour of CoCrMo Alloy Nitrided Utilising a HIPIMS Discharge
CoCrMo alloy specimens were plasma nitrided using a High Power Impulse Magnetron
Sputtering (HIPIMS) discharge. In this work the effect of nitriding voltage (-700 V to -1100
V) on the microstructure, surface hardness, impact load fatigue resistance and fracture
toughness (KIc) of the alloy has been investigated.
Results revealed that the specimens treated at lower nitriding voltages (-700 V and -900 V)
develop a nitrided layer consisting a mixture of Co4N+Co2-3N phases. As the nitriding
voltage increased (-1000 V and -1100 V), this transformed into a thick layer consisting
mainly of Co2-3N with a minor contribution from CrN/Cr2N phases. Accordingly, surface
hardness tests after nitriding showed a significant improvement in hardness value (H= 23
GPa) as compared to the untreated specimen, (H= 7.9 GPa). The impact resistance of the
alloy also increased with the nitriding voltage. Impact crater profiling of the specimens
subjected to impact load tests showed that the depth of the crater decreased significantly,
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especially at higher nitriding voltages. At the end of the impact load test (one million
impacts), the crater depth for an untreated alloy (12.78 Îźm) was found to be twice to the
crater depth measured for the specimen nitrided at -1100 V (7.1 Îźm). Impact testing results
indicate that the fatigue endurance limit of the CoCrMo alloy increased steadily and
considerably with the increase of the nitriding voltage. HIPIMS plasma nitriding resulted in a
layer material with improved plain strain fracture toughness (KIc), with higher values (KIc) =
1011 MPamm1/2 (-700 V specimen) were calculated as compared to KIc = 908 MPamm1/2 for
the untreated specimens. Critical material parameter ratios such as H/E (elastic index or
elastic strain to failure) and H3/E2 (plastic index) of the nitrided layers were calculated using
surface hardness (H) and elastic modulus (E) values obtained with the help of
nanoindentation tests. Systematic improvement in the values of H/E and H3/E2 ratios
calculated for all nitrided specimens validated the increase in fracture toughness and impact
load fatigue resistance of the nitrided specimens as compared to the corresponding properties
of the untreated CoCrMo base alloy
Thinking about Eating Food Activates Visual Cortex with Reduced Bilateral Cerebellar Activation in Females with Anorexia Nervosa: An fMRI Study
Background: Women with anorexia nervosa (AN) have aberrant cognitions about food and altered activity in prefrontal cortical and somatosensory regions to food images. However, differential effects on the brain when thinking about eating food between healthy women and those with AN is unknown. Methods: Functional magnetic resonance imaging (fMRI) examined neural activation when 42 women thought about eating the food shown in images: 18 with AN (11 RAN, 7 BPAN) and 24 age-matched controls (HC). Results: Group contrasts between HC and AN revealed reduced activation in AN in the bilateral cerebellar vermis, and increased activation in the right visual cortex. Preliminary comparisons between AN subtypes and healthy controls suggest differences in cortical and limbic regions. Conclusions: These preliminary data suggest that thinking about eating food shown in images increases visual and prefrontal cortical neural responses in females with AN, which may underlie cognitive biases towards food stimuli and ruminations about controlling food intake. Future studies are needed to explicitly test how thinking about eating activates restraint cognitions, specifically in those with restricting vs. binge-purging AN subtypes
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