| 1. |
- Fomalont, E. B., et al.
(author)
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THE 2014 ALMA LONG BASELINE CAMPAIGN: AN OVERVIEW
- 2015
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In: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 808:1
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Journal article (peer-reviewed)abstract
- A major goal of the Atacama Large Millimeter/submillimeter Array (ALMA) is to make accurate images with resolutions of tens of milliarcseconds, which at submillimeter (submm) wavelengths requires baselines up to similar to 15 km. To develop and test this capability, a Long Baseline Campaign (LBC) was carried out from 2014 September to late November, culminating in end-to-end observations, calibrations, and imaging of selected Science Verification (SV) targets. This paper presents an overview of the campaign and its main results, including an investigation of the short-term coherence properties and systematic phase errors over the long baselines at the ALMA site, a summary of the SV targets and observations, and recommendations for science observing strategies at long baselines. Deep ALMA images of the quasar 3C 138 at 97 and 241 GHz are also compared to VLA 43 GHz results, demonstrating an agreement at a level of a few percent. As a result of the extensive program of LBC testing, the highly successful SV imaging at long baselines achieved angular resolutions as fine as 19 mas at similar to 350 GHz. Observing with ALMA on baselines of up to 15 km is now possible, and opens up new parameter space for submm astronomy.
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| 2. |
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| 3. |
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| 4. |
- Bett, Cyrus, et al.
(author)
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Defining the Conformational Features of Anchorless, Poorly Neuroinvasive Prions
- 2013
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In: PLoS Pathogens. - : Public Library of Science. - 1553-7366 .- 1553-7374. ; 9:4
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Journal article (peer-reviewed)abstract
- Infectious prions cause diverse clinical signs and form an extraordinary range of structures, from amorphous aggregates to fibrils. How the conformation of a prion dictates the disease phenotype remains unclear. Mice expressing GPI-anchorless or GPI-anchored prion protein exposed to the same infectious prion develop fibrillar or nonfibrillar aggregates, respectively, and show a striking divergence in the disease pathogenesis. To better understand how a prion's physical properties govern the pathogenesis, infectious anchorless prions were passaged in mice expressing anchorless prion protein and the resulting prions were biochemically characterized. Serial passage of anchorless prions led to a significant decrease in the incubation period to terminal disease and altered the biochemical properties, consistent with a transmission barrier effect. After an intraperitoneal exposure, anchorless prions were only weakly neuroinvasive, as prion plaques rarely occurred in the brain yet were abundant in extracerebral sites such as heart and adipose tissue. Anchorless prions consistently showed very high stability in chaotropes or when heated in SDS, and were highly resistant to enzyme digestion. Consistent with the results in mice, anchorless prions from a human patient were also highly stable in chaotropes. These findings reveal that anchorless prions consist of fibrillar and highly stable conformers. The additional finding from our group and others that both anchorless and anchored prion fibrils are poorly neuroinvasive strengthens the hypothesis that a fibrillar prion structure impedes efficient CNS invasion.
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| 5. |
- Toro-Dominguez, D, et al.
(author)
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Differential Treatments Based on Drug-induced Gene Expression Signatures and Longitudinal Systemic Lupus Erythematosus Stratification
- 2019
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 15502-
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Journal article (peer-reviewed)abstract
- Systemic lupus erythematosus (SLE) is a heterogeneous disease with unpredictable patterns of activity. Patients with similar activity levels may have different prognosis and molecular abnormalities. In this study, we aimed to measure the main differences in drug-induced gene expression signatures across SLE patients and to evaluate the potential for clinical data to build a machine learning classifier able to predict the SLE subset for individual patients. SLE transcriptomic data from two cohorts were compared with drug-induced gene signatures from the CLUE database to compute a connectivity score that reflects the capability of a drug to revert the patient signatures. Patient stratification based on drug connectivity scores revealed robust clusters of SLE patients identical to the clusters previously obtained through longitudinal gene expression data, implying that differential treatment depends on the cluster to which patients belongs. The best drug candidates found, mTOR inhibitors or those reducing oxidative stress, showed stronger cluster specificity. We report that drug patterns for reverting disease gene expression follow the cell-specificity of the disease clusters. We used 2 cohorts to train and test a logistic regression model that we employed to classify patients from 3 independent cohorts into the SLE subsets and provide a clinically useful model to predict subset assignment and drug efficacy.
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| 6. |
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| 7. |
- Coutinho, P. M., et al.
(author)
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Post-genomic insights into the plant polysaccharide degradation potential of Aspergillus nidulans and comparison to Aspergillus niger and Aspergillus oryzae
- 2009
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In: Fungal Genetics and Biology. - : Elsevier BV. - 1096-0937 .- 1087-1845. ; 46:Suppl 1, s. S161-S169
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Journal article (peer-reviewed)abstract
- The plant polysaccharide degradative potential of Aspergillus nidulans was analysed in detail and compared to that of Aspergillus niger and Aspergillus oryzae using a combination of bioinformatics, physiology and transcriptomics. Manual verification indicated that 28.4% of the A. nidulans ORFs analysed in this study do not contain a secretion signal, of which 40% may be secreted through a non-classical method. While significant differences were found between the species in the numbers of ORFs assigned to the relevant CAZy families, no significant difference was observed in growth on polysaccharides. Growth differences were observed between the Aspergilli and Podospora anserina, which has a more different genomic potential for polysaccharide degradation, suggesting that large genomic differences are required to cause growth differences oil polysaccharides, Differences were also detected between the Aspergilli in the presence Of putative regulatory sequences in the promoters of the ORFs Of this Study and correlation of the presence Of putative XlnR binding sites to induction by xylose was detected for A. niger. These data demonstrate differences at genome content, Substrate specificity of the enzymes and gene regulation in these three Aspergilli, which likely reflect their individual adaptation to their natural biotope. (C) 2008 Elsevier Inc. All rights reserved.
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| 8. |
- Egan, Allyson C, et al.
(author)
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The Sound of Interconnectivity; The European Vasculitis Society 2022 Report
- 2022
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In: Kidney International Reports. - : Elsevier BV. - 2468-0249. ; 7:8, s. 1745-1757
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Journal article (peer-reviewed)abstract
- The first European Vasculitis Society (EUVAS) meeting report was published in 2017. Herein, we report on developments in the past 5 years which were greatly influenced by the pandemic. The adaptability to engage virtually, at this critical time in society, embodies the importance of networks and underscores the role of global collaborations. We outline state-of-the-art webinar topics, updates on developments in the last 5 years, and proposals for agendas going forward. A host of newly reported clinical trials is shaping practice on steroid minimization, maintenance strategies, and the role of newer therapies. To guide longer-term strategies, a longitudinal 10-year study investigating relapse, comorbidity, malignancy, and survival rates is at an advanced stage. Disease assessment studies are refining classification criteria to differentiate forms of vasculitis more fully. A large international validation study on the histologic classification of anti-neutrophil cytoplasmic antibody (ANCA) glomerulonephritis, recruiting new multicenter sites and comparing results with the Kidney Risk Score, has been conducted. Eosinophilic granulomatosis with polyangiitis (EGPA) genomics offers potential pathogenic subset and therapeutic insights. Among biomarkers, ANCA testing is favoring immunoassay as the preferred method for diagnostic evaluation. Consolidated development of European registries is progressing with an integrated framework to analyze large clinical data sets on an unprecedented scale.
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| 9. |
- Iglesias-Carrasco, Maider, et al.
(author)
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An experimental test for body size-dependent effects of male harassment and an elevated copulation rate on female lifetime fecundity and offspring performance
- 2019
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In: Journal of Evolutionary Biology. - : Wiley. - 1010-061X .- 1420-9101. ; 32:11, s. 1262-1273
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Journal article (peer-reviewed)abstract
- Many studies investigate the benefits of polyandry, but repeated interactions with males can lower female reproductive success. Interacting with males might even decrease offspring performance if it reduces a female's ability to transfer maternal resources. Male presence can be detrimental for females in two ways: by forcing females to mate at a higher rate and through costs associated with resisting male mating attempts. Teasing apart the relative costs of elevated mating rates from those of greater male harassment is critical to understand the evolution of mating strategies. Furthermore, it is important to test whether a male's phenotype, notably body size, has differential effects on female reproductive success versus the performance of offspring, and whether this is due to male body size affecting the costs of harassment or the actual mating rate. In the eastern mosquitofish Gambusia holbrooki, males vary greatly in body size and continually attempt to inseminate females. We experimentally manipulated male presence (i.e., harassment), male body size and whether males could copulate. Exposure to males had strong detrimental effects on female reproductive output, growth and immune response, independent of male size or whether males could copulate. In contrast, there was a little evidence of a cross-generational effect of male harassment or mating rate on offspring performance. Our results suggest that females housed with males pay direct costs due to reduced condition and offspring production and that these costs are not a consequence of increased mating rates. Furthermore, exposure to males does not affect offspring reproductive traits.
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| 10. |
- Mitchell, David J., et al.
(author)
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Experimental translocations to low predation lead to non-parallel increases in relative brain size
- 2020
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In: Biology Letters. - : The Royal Society. - 1744-9561 .- 1744-957X. ; 16:1
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Journal article (peer-reviewed)abstract
- Predation is a near ubiquitous factor of nature and a powerful selective force on prey. Moreover, it has recently emerged as an important driver in the evolution of brain anatomy, though population comparisons show ambiguous results with considerable unexplained variation. Here, we test the reproducibility of reduced predation on evolutionary trajectories of brain evolution. We make use of an introduction experiment, whereby guppies (Poecilia reticulata) from a single high predation stream were introduced to four low predation streams. After 8-9 years of natural selection in the wild and two generations of common garden conditions in the laboratory, we quantified brain anatomy. Relative brain region sizes did not differ between populations. However, we found a general increase and striking variation in relative brain size of introduced populations, which varied from no change to a 12.5% increase in relative brain weight, relative to the ancestral high predation population. We interpret this as evidence for non-parallel evolution, which implies a weak or inconsistent association of relative brain size with fitness in low predation sites. The evolution of brain anatomy appears sensitive to unknown environmental factors, or contingent on either chance events or historical legacies of environmental change.
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| 11. |
- Patxot, Marion, et al.
(author)
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Probabilistic inference of the genetic architecture underlying functional enrichment of complex traits
- 2021
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Journal article (peer-reviewed)abstract
- We develop a Bayesian model (BayesRR-RC) that provides robust SNP-heritability estimation, an alternative to marker discovery, and accurate genomic prediction, taking 22 seconds per iteration to estimate 8.4 million SNP-effects and 78 SNP-heritability parameters in the UK Biobank. We find that only ≤10% of the genetic variation captured for height, body mass index, cardiovascular disease, and type 2 diabetes is attributable to proximal regulatory regions within 10kb upstream of genes, while 12-25% is attributed to coding regions, 32–44% to introns, and 22-28% to distal 10-500kb upstream regions. Up to 24% of all cis and coding regions of each chromosome are associated with each trait, with over 3,100 independent exonic and intronic regions and over 5,400 independent regulatory regions having ≥95% probability of contributing ≥0.001% to the genetic variance of these four traits. Our open-source software (GMRM) provides a scalable alternative to current approaches for biobank data.
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| 12. |
- Steffan, Adrian, et al.
(author)
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Validation of an open source, remote web-based eye-tracking method (WebGazer) for research in early childhood
- 2024
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In: Infancy. - 1525-0008 .- 1532-7078. ; 29:1
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Journal article (peer-reviewed)abstract
- Measuring eye movements remotely via the participant's webcam promises to be an attractive methodological addition to in-person eye-tracking in the lab. However, there is a lack of systematic research comparing remote web-based eye-tracking with in-lab eye-tracking in young children. We report a multi-lab study that compared these two measures in an anticipatory looking task with toddlers using WebGazer.js and jsPsych. Results of our remotely tested sample of 18-27-month-old toddlers (N=125) revealed that web-based eye-tracking successfully captured goal-based action predictions, although the proportion of the goal-directed anticipatory looking was lower compared to the in-lab sample (N=70). As expected, attrition rate was substantially higher in the web-based (42%) than the in-lab sample (10%). Excluding trials based on visual inspection of the match of time-locked gaze coordinates and the participant's webcam video overlayed on the stimuli was an important preprocessing step to reduce noise in the data. We discuss the use of this remote web-based method in comparison with other current methodological innovations. Our study demonstrates that remote web-based eye-tracking can be a useful tool for testing toddlers, facilitating recruitment of larger and more diverse samples; a caveat to consider is the larger drop-out rate.
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| 13. |
- Vega-Trejo, Regina, et al.
(author)
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Predation impacts brain allometry in female guppies (Poecilia reticulata)
- 2022
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In: Evolutionary Ecology. - : Springer Science and Business Media LLC. - 0269-7653 .- 1573-8477. ; 36:6, s. 1045-1059
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Journal article (peer-reviewed)abstract
- Cognitive and sensory abilities are vital in affecting survival under predation risk, leading to selection on brain anatomy. However, how exactly predation and brain evolution are linked has not yet been resolved, as current empirical evidence is inconclusive. This may be due to predation pressure having different effects across life stages and/or due to confounding factors in ecological comparisons of predation pressure. Here, we used adult guppies (Poecilia reticulata) to experimentally test how direct predation during adulthood would impact the relative brain size and brain anatomy of surviving individuals to examine if predators selectively remove individuals with specific brain morphology. To this end, we compared fish surviving predation to control fish, which were exposed to visual and olfactory predator cues but could not be predated on. We found that predation impacted the relative size of female brains. However, this effect was dependent on body size, as larger female survivors showed relatively larger brains, while smaller survivors showed relatively smaller brains when compared to control females. We found no differences in male relative brain size between survivors and controls, nor for any specific relative brain region sizes for either sex. Our results corroborate the important, yet complex, role of predation as an important driver of variation in brain size.
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| 14. |
- Vega-Trejo, Regina, et al.
(author)
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The effects of male age, sperm age and mating history on ejaculate senescence
- 2019
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In: Functional Ecology. - : Wiley. - 0269-8463 .- 1365-2435. ; 33:7, s. 1267-1279
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Journal article (peer-reviewed)abstract
- 1. In polyandrous species, a male's reproductive success depends on his ability to fertilize females, which, in turn, depends on his mating ability and his ability to produce competitive ejaculates. In many species, sperm traits differ between old and young males in ways that are likely to decrease the sperm competitiveness and fertility of older males. This age-ejaculate quality relationship is attributed to male ageing (i.e., senescence). 2. In a natural setting, male age and mating history are usually confounded: older males have usually mated and replenished their sperm supplies more often, so they have made a greater lifetime reproductive effort. In principle, the costs of reproduction, independent of any causal effect of male age, could generate an age-related decline in ejaculate quality. 3. To date, only a handful of studies have determined how male age, reproductive effort or their interaction affect ejaculate quality. Here, we experimentally manipulated the long-term mating history of 209 adult male mosquitofish (Gambusia holbrooki) over 14 weeks (N = 1,118 sperm samples). Males either had direct access to females and could mate freely, or had only visual and olfactory access to females. We documented the effect of mating history, adult male age (3, 9 and 14 weeks post-maturation) and their interaction on sperm velocity, sperm reserves and the rate of sperm replenishment. For sperm velocity, we additionally examined the effects of sperm age, because when older males mate less (or more) often than younger males there will be a correlation between mean sperm age and male age. 4. Sexually active males produced fewer sperm and replenished their sperm at a lower rate, and their sperm had lower velocity than males prevented from mating. Though older males produced more sperm, the rate of replenishment and velocity of their sperm was lower than the sperm of younger males. We also tested for a difference in the velocity of recently replenished (<24 hr) and older sperm (i.e., post-meiotic sperm senescence). There was no evidence that male age or mating history affects the extent of sperm senescence, but older sperm swam faster than recently produced sperm. Crucially, complex interactions are evident between male age and male mating history with respect to sperm number and the proportion of sperm that are replenished. 5. These results suggest that male age and mating history will interact to determine the reproductive success of a male under sperm competition. They reveal a complex relationship between a male's age and his ejaculate quality. We suggest that both mating history and sperm age should be controlled for when measuring the intrinsic rate of senescence for male reproductive traits if the goal is to isolate effects that are solely attributable to a male's chronological age.
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| 15. |
- Vila Pouca, Catarina, et al.
(author)
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Early predation risk shapes adult learning and cognitive flexibility
- 2021
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In: Oikos. - : Wiley. - 0030-1299 .- 1600-0706. ; 130:9, s. 1477-1486
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Journal article (peer-reviewed)abstract
- Predation risk during early ontogeny can impact developmental trajectories and permanently alter adult phenotypes. Such phenotypic plasticity often leads to adaptive changes in traits involved in anti-predator responses. While plastic changes in cognition may increase survival, it remains unclear whether early predation experience shapes cognitive investment and drives developmental plasticity in cognitive abilities. Here, we show that predation risk during early ontogeny induces developmental plasticity in two cognitive domains. We reared female guppies Poecilia reticulata with and without predator cues and tested their adult cognitive abilities. We found that females reared under simulated predation took longer to learn a simple association task, yet outperformed animals reared without predation threat in a reversal learning task testing cognitive flexibility. These results show that predation pressure during ontogeny shapes adult cognitive abilities, which we argue is likely to be adaptive. Our study highlights the important role of predator-mediated developmental plasticity on cognitive investment in natural populations and the general role of plasticity in cognitive performance.
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| 16. |
- Watanabe, Ryo R., et al.
(author)
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Rotary properties of hybrid F1-ATPases consisting of subunits from different species
- 2023
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In: iScience. - 2589-0042. ; 26:5
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Journal article (peer-reviewed)abstract
- F-1-ATPase (F-1) is an ATP-driven rotary motor protein ubiquitously found in many species as the catalytic portion of FoF1-ATP synthase. Despite the highly conserved amino acid sequence of the catalytic core subunits: alpha and beta, F-1 shows diversity in the maximum catalytic turnover rate V-max and the number of rotary steps per turn. To study the design principle of F-1, we prepared eight hybrid F(1)s composed of subunits from two of three genuine (F)1s: thermophilic Bacillus PS3 (TF1), bovine mitochondria (bMF(1)), and Paracoccus denitrificans (PdF1), differing in the V-max and the number of rotary steps. The V-max of the hybrids can be well fitted by a quadratic model highlighting the dominant roles of 0 and the couplings between alpha-beta. Although there exist no simple rules on which subunit dominantly determines the number of steps, our findings show that the stepping behavior is characterized by the combination of all subunits.
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